Acoustofluidic lysis of cancer cells and Raman spectrum profiling.
The lysis of cancer cells inside a sessile droplet was performed using traveling surface acoustic waves (SAWs) without any chemical reagents. Raman spectrum profiling was then carried out to explore detailed cell-derived data. The Rayleigh waves formed by an interdigital transducer were made to propagate along the surface of an LiNbO3 substrate. Polystyrene microparticles (PSMPs) were used to establish mechanical cell lysis effectively, and gold nanoparticles (AuNPs) were added to enhance the Raman signals from the lysed cells by SAWs. The lysis efficiency was evaluated according to the size and concentration of the PSMPs in experiments where the frequency was varied. Lysis occurred mainly by mechanical collision using PSMPs in a high-frequency domain, and the lysis efficiency was improved by increasing the application time and the energy density of the SAWs. Raman signals from the lysed cells were greatly enhanced by nanogaps formed by the AuNPs, which were evenly distributed irrespective of the SAWs through the frequency-independent behavior of the AuNPs. Finally, detailed Raman spectra of MDA-MB-231, malignant breast cancer cells, were acquired, and various organic matter-derived peaks were observed. The 95% confidence region for cells subjected to lysis was more widely distributed than that of cells not subjected to lysis. The proposed SAW platform is expected to facilitate the detection of small quantities and to be applied in biomedical applications.


Psychometric properties of the Swedish version of the Falls Efficacy Scale-International for older adults with osteoporosis, self-reported balance deficits and fear of falling.
Investigate the psychometric properties of the Swedish version of the Falls Efficacy Scale-International (FES-I). Cross-sectional study. Community-dwelling older adults with self-reported balance deficits and fear of falling were recruited from an ongoing randomised controlled study to evaluate the psychometric properties of the FES-I using Rasch model analysis. The Rasch model analysis revealed good category function, the questionnaire measured one dimension with an explained variance of 68.6% and item goodness-of-fit with mean square values (MnSq) 0.7-1.44. The item map showed that all items are spread over the scale, which indicates different difficulties in the items. Non-satisfactory person goodness-of-fit was shown with seven persons and showed person misfit according to both the MnSq-value and the z-value, 38 persons (40%) showed a person misfit when only following the threshold for MnSq. The Swedish version of FES-I shows good psychometric properties with unidimensionality and item goodness-of-fit. Lower person goodness-of-fit was shown probably because of confounding factors that may influence the answers. The transformed values of the FES-I make it possible to use parametric statistics preferable for this population in future research. Implications for rehabilitation The Falls Efficacy Scale-International (FES-I) shows good psychometric properties with unidimensionality, item goodness-of-fit and good item reliability, which means that FES-I is a valuable tool when measuring concerns about falling in an older population with osteoporosis and could be useful in clinical settings. Confounding factors such as pain, high number of falls, low fall self-efficacy, experience of previous falls, and vertigo may influence the answers and result in low person goodness-of-fit.


Light cells within the limiting membrane of rat seminiferous tubules.
Light-staining cells, distinct from myoid cells, were identified in electron micrographs of the limiting membrane of rat seminiferous tubules. While these cells were also found free in the interstitial space, they were observed mostly in the myoid cell layer of the limiting membrane but were never seen within the seminiferous epithelium itself. The light cells were characterized by a pale-stained cytoplasm containing a spheroidal Golgi apparatus next to a polymorphous often kidney-shaped nucleus, a few cisternae of rough endoplasmic reticulum and some granules of various types including a multivesicular bodies. In hematoxylin-stained whole mounts of dissected tubules, these light cells were readily identified under the light microscope by nuclear morphology and light-staining juxtanuclear Golgi apparatus. The incidence of these cells, per unit surface area of tubular wall, was calculated, taking into consideration the stages of the cylce of the seminiferous epithelium with which they were associated. Distributed along the entire length of seminiferous tubules, their number varied significantly during the cycle. Low numbers were found in stages II-IV and XIII of the cycle while high numbers were found in stages IX to XII and XIV-I of the cycle. These observations indicate that the seminiferous epithelium may exert an influence on the population of light cells present in the tubular limiting membrane.


Prognostic Importance of Changes in Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone.
Limited data exist regarding the impact of aldosterone antagonist therapy on cardiac structure and function in heart failure with preserved ejection fraction and on the prognostic relevance of changes in cardiac structure and function in heart failure with preserved ejection fraction. Cardiac structure and function were assessed by quantitative echocardiography at baseline and at 12- to 18-month follow-up in 239 patients with heart failure with preserved ejection fraction (left ventricular [LV] ejection fraction [LVEF] ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. The impact of spironolactone therapy on measures of cardiac structure and function was assessed in the study population overall, and change in echocardiographic measures was associated with the subsequent occurrence of the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest. Spironolactone was not associated with alterations in cardiac structure and function compared with placebo. Decrease in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary outcome. Twelve to 18 months of spironolactone therapy was not associated with alterations in cardiac structure or function in patients with heart failure with preserved ejection fraction. Reduction in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary composite outcome. URL: http:///www.clinicaltrials.gov. Unique identifier: NCT00094302.


Clinical significance of antibodies against tropomyosin, actin and myosin in patients with dilated cardiomyopathy.
In the present study we evaluated the importance of autoimmune mechanisms in dilated cardiomyopathies. Sera from 81 patients with dilated cardiomyopathy, 17 patients with various other cardiologic diseases and 40 apparently healthy blood donors were tested with an immunoassay method for the presence of autoantibodies against tropomyosin, myosin and actin, three antigens which are components of the cardiac tissue. Elevated values of autoantibodies were obtained in a high percentage of patients with dilated cardiomyopathy as compared to the control group (66% antitropomyosin IgG, 66% antimyosin IgG, 28.3% antitropomyosin IgM). It has also been shown, for the first time, that patients with dilated cardiomyopathy and positive for at least one of the screened autoantibodies had a thicker interventricular septum thickness, systolic and diastolic than patients negative for the presence of autoantibodies (1.18 +/- 0.3, 1.2 +/- 0.3 vs 0.88 +/- 0.1, 0.9 +/- 0.2 respectively), a finding that indicates the importance of these autoantibodies. Although further investigation is needed, it is concluded that the detection of these autoantibodies can be a useful tool for the diagnosis, follow-up and prognosis of the patients with dilated cardiomyopathy.


Task-shifting alcohol interventions for HIV+ persons in Kenya: a cost-benefit analysis.
Among HIV+ patients, alcohol use is a highly prevalent risk factor for both HIV transmission and poor adherence to HIV treatment. The large-scale implementation of effective interventions for treating alcohol problems remains a challenge in low-income countries with generalized HIV epidemics. It is essential to consider an intervention's cost-effectiveness in dollars-per-health-outcome, and the long-term economic impact -or "return on investment" in monetary terms. We conducted a cost-benefit analysis, measuring economic return on investment, of a task-shifted cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use in a modeled cohort of 13,440 outpatients in Kenya. In our base-case, we estimated the costs and economic benefits from a societal perspective across a six-year time horizon, with a 3% annual discount rate. Costs included all costs associated with training and administering task-shifted CBT therapy. Benefits included the economic impact of lowered HIV incidence as well as the improvements in household and labor-force productivity. We conducted univariate and multivariate probabilistic sensitivity analyses to test the robustness of our results. Under the base case, total costs for CBT rollout was $554,000, the value of benefits were $628,000, and the benefit-to-cost ratio was 1.13. Sensitivity analyses showed that under most assumptions, the benefit-to-cost ratio remained above unity indicating that the intervention was cost-saving (i.e., had positive return on investment). The duration of the treatment effect most effected the results in sensitivity analyses. CBT can be effectively and economically task-shifted to paraprofessionals in Kenya. The intervention can generate not only reductions in morbidity and mortality, but also economic savings for the health system in the medium and long term. The findings have implications for other countries with generalized HIV epidemics, high prevalence of alcohol consumption, and shortages of mental health professionals. This paper uses data derived from "Cognitive Behavioral Treatment to Reduce Alcohol Use Among HIV-Infected Kenyans (KHBS)" with ClinicalTrials.gov registration NCT00792519 on 11/17/2008; and preliminary data from "A Stage 2 Cognitive-behavioral Trial: Reduce Alcohol First in Kenya Intervention" ( NCT01503255 , registered on 12/16/2011).


Multiplexed detection of mycotoxins in foods with a regenerable array.
The occurrence of different mycotoxins in cereal products calls for the development of a rapid, sensitive, and reliable detection method that is capable of analyzing samples for multiple toxins simultaneously. In this study, we report the development and application of a multiplexed competitive assay for the simultaneous detection of ochratoxin A (OTA) and deoxynivalenol (DON) in spiked barley, cornmeal, and wheat, as well as in naturally contaminated maize samples. Fluoroimmunoassays were performed with the Naval Research Laboratory array biosensor, by both a manual and an automated version of the system. This system employs evanescent-wave fluorescence excitation to probe binding events as they occur on the surface of a waveguide. Methanolic extracts of the samples were diluted threefold with buffer containing a mixture of fluorescent antibodies and were then passed over the arrays of mycotoxins immobilized on a waveguide. Fluorescent signals of the surface-bound antibody-antigen complexes decreased with increasing concentrations of free mycotoxins in the extract. After sample analysis was completed, surfaces were regenerated with 6 M guanidine hydrochloride in 50 mM glycine, pH 2.0. The limits of detection determined by the manual biosensor system were as follows: 1, 180, and 65 ng/g for DON and 1, 60, and 85 ng/g for OTA in cornmeal, wheat, and barley, respectively. The limits of detection in cornmeal determined with the automated array biosensor were 15 and 150 ng/g for OTA and DON, respectively.


Camera-based single-molecule FRET detection with improved time resolution.
The achievable time resolution of camera-based single-molecule detection is often limited by the frame rate of the camera. Especially in experiments utilizing single-molecule Förster resonance energy transfer (smFRET) to probe conformational dynamics of biomolecules, increasing the frame rate by either pixel-binning or cropping the field of view decreases the number of molecules that can be monitored simultaneously. Here, we present a generalised excitation scheme termed stroboscopic alternating-laser excitation (sALEX) that significantly improves the time resolution without sacrificing highly parallelised detection in total internal reflection fluorescence (TIRF) microscopy. In addition, we adapt a technique known from diffusion-based confocal microscopy to analyse the complex shape of FRET efficiency histograms. We apply both sALEX and dynamic probability distribution analysis (dPDA) to resolve conformational dynamics of interconverting DNA hairpins in the millisecond time range.


Radio-nanomaterials for biomedical applications: state of the art.
The incorporation of radioactive isotope(s) into conventional nanomaterials can bring extra properties which are not possessed by original materials. The resulting radioactive nanomaterials (radio-nanomaterials), with added physical/chemical properties, can be used as important tools for different biomedical applications. In this review, our goal is to provide an up-to-date overview on these applications using radio-nanomaterials. The first section illustrates the utilization of radionanomaterials for understanding of in vivo kinetics of their parent nano-materials. In the second section, we focus on two primary applications of radio-nanomaterials: imaging and therapeutic delivery. With various methods being used to form radio-nanomaterials, they can be used for positron emission tomography (PET), single-photon emission computed tomography (SPECT), and multimodal imaging. Therapeutic isotopes-loading radio-nanomaterials can possess selective killing efficacy of diseased cells (e.g. tumor cells) and can provide promises for certain isotopes which are not able to be used in a conventional manner. The successful and versatile biomedical applications of radio-nanomaterials warrants further investigations of those materials and their optimizations can pave the way to future imaging guidable, personalized treatments in patients.


Identification of genes associated with metastasis of mammary carcinoma in metastatic versus non-metastatic cell lines.
Cell lines 4A4 and 2C5 are the respective metastatic and non-metastatic variants (nude mouse system) derived from the human mammary carcinoma cell line MDA-MB-435. In order to identify genes associated with or functionally involved in metastasis, we have extended our previous transcriptional profile from 5000 to 12,000 genes using the Affymetrix Gene Chip array technology. Based on a threshold level of a change factor of > or = 2.5, we found that the steady-state level of 40 genes (0.3%) was up-regulated and conversely 89 genes (0.7%) were down-regulated in the metastatic cell line 4A4. The de-regulated genes were classified into categories such as tumor antigens/transmembrane receptors, enzymes, mediators of signaling, cell migration and angiogenesis, cell-cycle-, apoptosis-, differentiation- and growth-factor related genes, tumor suppression, transcription factors and genes encoding components of the extracellular matrix and the cytoskeleton. As possible mediators of invasion we identified DGCR6, osteopontin, autotaxin and the 65 kD phosphoprotein p65. In addition, three sugar-modifying enzymes were up-regulated in cell line 4A4. Profound differences in G-protein-mediated signaling and down-regulation of the tumor-suppressor genes DPC4, BARDI and DLC-1 were noted in the metastatic cell line 4A4.


Resveratrol ameliorates high glucose and high-fat/sucrose diet-induced vascular hyperpermeability involving Cav-1/eNOS regulation.
Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation.


Sigma1 receptor antagonists determine the behavioral pattern of the methamphetamine-induced stereotypy in mice.
The effects of sigma receptor antagonists on methamphetamine (METH)-induced stereotypy have not been examined. We examined the effects of sigma antagonists on METH-induced stereotypy in mice. The administration of METH (10 mg/kg) to male ddY mice induced stereotyped behavior consisting of biting (90.1%), sniffing (4.2%), head bobbing (4.1%), and circling (1.7%) during an observation period of 1 h. Pretreatment of the mice with BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol; 1, 5, and 10 mg/kg), a non-specific sigma receptor antagonist, significantly increased METH-induced sniffing (19.2%, 30.5%, and 43.8% of total stereotypical behavior) but decreased biting (76.6%, 66.9%, and 49.3% of total stereotypical behavior) in a dose-dependent manner. This response was completely abolished by (+)-SKF 10,047 ([2S-(2alpha,6alpha,11R)]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol; 4 and 10 mg/kg), a putative sigma(1) receptor agonist, and partially by PB 28 (1-cyclohexyl-4-[3-(1,2,3,4-tetrahydro-5-methoxy-1-naphthalen-1-yl)-n-propyl]piperazine; 1 and 10 mg/kg), a putative sigma(2) receptor agonist. The BMY 14802 action on METH-induced stereotypy was mimicked by BD 1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine; 10 mg/kg), a putative sigma(1) receptor antagonist, but not by SM-21 ((+/-)-tropanyl 2-(4-chlorophenoxy)butanoate; 1 mg/kg), a putative sigma(2) receptor antagonist. The BD 1047 effect on METH-induced stereotypy was also abolished completely by (+)-SKF 10,047 and partially by PB 28. The overall frequency of METH-induced stereotypical behavior was unchanged with these sigma receptor ligands, despite the alteration in particular behavioral patterns. The BMY 14802 action on METH-induced stereotypy was unaffected by pretreatment with centrally acting histamine H(1) receptor antagonists (pyrilamine or ketotifen, 10 mg/kg), suggesting that these effects are independent of histamine H(1) receptor signaling systems. In summary, modulation of central sigma(1) receptors alters the pattern of METH-induced stereotypy, producing a shift from stereotypical biting to stereotypical sniffing, without affecting the overall frequency of stereotypical behavior.


Combination therapy of Chinese herbal medicine Fructus Ligustri Lucidi with high calcium diet on calcium imbalance induced by ovariectomy in mice.
Our previous biological study demonstrated that Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait. (Oleaceae), could be used to maintain calcium balance and prevent age-related osteoporosis since it effectively decreased calcium loss and increased calcium retention in rats. This study investigates the combination effect of the Chinese herbal medicine FLL and a high calcium diet on calcium imbalance induced by ovariectomy in mice. The ovariectomized (OVX) mice were orally treated with vehicle, FLL extract (700 mg/kg), milk powder (5 g/mice) fortified with calcium (1.0% Ca) and the combination of FLL with milk powder. After 6 weeks of treatment, urine, serum, and tibia were preserved for biochemical analysis and kidneys were taken for gene expression analysis. The combination treatment of FLL and a high calcium diet significantly increased bone calcium content (6.80 ± 0.34 mg) by 22% (p < 0.05) and decreased urine calcium excretion (0.099 ± 0.009 mg/mg) by 62% (p < 0.01) as compared with those of the OVX group (bone Ca, 5.57 ± 0.31 mg; urine Ca/Cr, 0.261 ± 0.017 mg/mg). The mRNA expression of renal calcium-binding protein-9k (CaBP-9k) and calcium-sensing receptor (CaSR) in combination treatment group was significantly up-regulated and down-regulated, respectively, as compared with those of the OVX group. The beneficial effects of this combination therapy on calcium balance of OVX mice were, at least partially, attributed to its regulation on mRNA expression of CaBP-9k and CaSR in kidney.


Extinction coefficient of gold nanoparticles with different sizes and different capping ligands.
Extinction coefficients of gold nanoparticles with core size ranging from approximately 4 to 40 nm were determined by high resolution transmission electron microscopy analysis and UV-vis absorption spectroscopic measurement. Three different types of gold nanoparticles were prepared and studied: citrate-stabilized nanoparticles in five different sizes; oleylamide-protected gold nanoparticles with a core diameter of 8 nm, and a decanethiol-protected nanoparticle with a diameter of around 4 nm. A linear relationship between the logarithms of extinction coefficients and core diameters of gold particles was found independent of the capping ligands on the particle surface and the solvents used to dissolve the nanoparticles. This linear relation may be used as a calibration curve to determine the concentration or average size of an unknown nanoparticle or nanoparticle-biomolecule conjugate sample.


Diastereomerically Differentiated Excited State Behavior in Ruthenium(II) Hexafluoroacetylacetonate Complexes of Diphenyl Thioindigo Diimine.
Mono- and diruthenium hexafluoroacetylacetonate (hfac) complexes of the thioindigo-N,N'-diphenyldiimine chelating ligand 3 have been prepared. The thioindigo diimine ligand binds to ruthenium in a bidentate fashion in the mononuclear compound 2 and serves as a bidentate chelating bridging ligand in the diruthenium complexes 1a and 1b. Compound 2 was isolated as a racemic mixture while the diruthenium complexes were isolated as the meso (ΔΛ) 1a and rac (ΔΔ and ΛΛ) 1b diastereomers. In-depth structural characterization of the compounds was performed, including X-ray crystallography, 1H, 13C, and 19F nuclear magnetic resonance (NMR) spectroscopy, and 2D NMR correlation experiments. Electrochemical properties were evaluated utilizing cyclic voltammetry. Ground state optical properties of the complexes were examined using UV-visible spectroscopy and spectroelectrochemistry. The excited state dynamics of the series were investigated by ultrafast transient absorption spectroscopy. Variable temperature NMR experiments demonstrated that the rac diruthenium compound 1b undergoes conformational exchange with a rate constant of 8700 s-1 at 298 K, a behavior that is not observed in the meso diastereomer 1a. The series of complexes possess metal-to-ligand charge transfer (MLCT) absorption bands in the near-infrared (λmax 689-783 nm). The compounds do not display photoluminescence in room temperature solution-phase experiments or in experiments at 77 K. Transient absorption spectroscopy measurements revealed excited states with picosecond lifetimes for 1a, 1b, and 2, and spectroelectrochemical experiments confirmed assignment of the transient species as arising from MLCT transitions. Unexpectedly, the transient absorption measurements revealed disparate time constants for the excited state decay of diastereomers 1a and 1b.


Involvement of reactive oxygen species and glutathione in gallic acid-induced human umbilical vein endothelial cell death.
Gallic acid (GA) has various biological effects including apoptosis. In this study, we investigated the effects of GA on human primary umbilical vein endothelial cells (HUVECs) in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH). Treatment with 200 or 400 µM GA inhibited the growth of HUVECs at 24 h and induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; ∆Ψm). GA decreased or increased ROS levels including O2•-. It dose-dependently increased GSH depleted cell numbers. Pan-caspase inhibitor (Z-VAD) did not affect cell growth inhibition, cell death, ROS and GSH levels in GA-treated HUVECs. However, N-acetyl-cysteine (NAC; a well known antioxidant) and L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) enhanced cell growth inhibition, cell death and MMP (∆Ψm) loss in GA-treated HUVECs. NAC decreased general ROS levels in GA-treated HUVECs, but strongly increased O2•- levels in these cells. Both NAC and BSO intensified the GSH depletion of GA-treated HUVECs. In conclusion, GA treatment induced growth inhibition and death of HUVECs. The changes of ROS and GSH levels by NAC and BSO influenced cell growth and death in GA-treated HUVECs.


Peptide YY3-36 and 5-hydroxytryptamine mediate emesis induction by trichothecene deoxynivalenol (vomitoxin).
Deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin produced by Fusarium sp. that frequently occurs in cereal grains, has been associated with human and animal food poisoning. Although a common hallmark of DON-induced toxicity is the rapid onset of emesis, the mechanisms for this adverse effect are not fully understood. Recently, our laboratory has demonstrated that the mink (Neovison vison) is a suitable small animal model for investigating trichothecene-induced emesis. The goal of this study was to use this model to determine the roles of two gut satiety hormones, peptide YY3-36 (PYY3-36) and cholecystokinin (CCK), and the neurotransmitter 5-hydroxytryptamine (5-HT) in DON-induced emesis. Following ip exposure to DON at 0.1 and 0.25mg/kg bw, emesis induction ensued within 15-30min and then persisted up to 120min. Plasma DON measurement revealed that this emesis period correlated with the rapid distribution and clearance of the toxin. Significant elevations in both plasma PYY3-36 (30-60min) and 5-HT (60min) but not CCK were observed during emesis. Pretreatment with the neuropeptide Y2 receptor antagonist JNJ-31020028 attenuated DON- and PYY-induced emesis, whereas the CCK1 receptor antagonist devezapide did not alter DON's emetic effects. The 5-HT3 receptor antagonist granisetron completely suppressed induction of vomiting by DON and the 5-HT inducer cisplatin. Granisetron pretreatment also partially blocked PYY3-36-induced emesis, suggesting a potential upstream role for this gut satiety hormone in 5-HT release. Taken together, the results suggest that both PYY3-36 and 5-HT play contributory roles in DON-induced emesis.


Anesthetic management of patient with Sjogren's syndrome who underwent cesarean section: a case report.
Sjogren's syndrome is one of the most common autoimmune disorders and has a female predominance. Maternal circulating autoantibodies such as anti-Ro/SSA and anti-La/SSB antibodies can cause congenital heart block of fetus, and in severe case, emergency pacemaker implantation may be needed for neonate. Therefore, it is very important to understand maternal and fetal condition and pay attention to the status of the neonate during delivery. In this paper, we present a case of patient with Sjogren's syndrome who underwent cesarean section under spinal anesthesia.


Isolated gallbladder injury in a case of blunt abdominal trauma.
The diagnosis of blunt injury to the gallbladder may constitute a significant challenge to the diagnostician. There is often a delay in presentation with non-specific clinical symptoms. In the absence of reliable clinical symptoms, diagnostic imaging becomes an invaluable tool in the rapid identification of gallbladder injury. We present a case of isolated gallbladder injury following blunt abdominal trauma which was diagnosed by computed tomography and subsequently confirmed by cholecystectomy.


Nicotinamide prevents N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in Sprague-Dawley rats and C57BL mice.
In previous studies, it was found that a single systemic administration of N-methyl-N-nitrosourea (MNU) to rats and mice resulted in the retinal degeneration in all treated animals over a 7 day period. Retinal degeneration was due to photoreceptor cell apoptosis that was identical to the apoptosis seen in human retinitis pigmentosa (RP). In the present study, nicotinamide (NAM), a water-soluble B-group vitamin (vitamin B(3)), suppressed photoreceptor cell loss in a dose-dependent manner when administered immediately after MNU treatment. In rats, a dose of NAM >or=25 mg kg(-1) completely suppressed photoreceptor cell loss, and 10 mg kg(-1) partially suppressed photoreceptor cell loss. In mice, doses of 1000 and >or=100 mg kg(-1) were needed for complete and partial suppression, respectively. Thus, rats were more responsive to NAM than mice. The retinoprotective effect of 1000 mg kg(-1) NAM lasted throughout the long-term (35 days) observation period, with no apparent toxicity. Also, in rats, 1000 mg kg(-1) NAM completely suppressed photoreceptor cell loss when administered up to 4 hr after MNU treatment, and partially suppressed photoreceptor cell loss when administered 6 hr after MNU treatment. In mice, administration of NAM 2-6 hr after MNU resulted in partial suppression. NAM did not reduce levels of 7-methyldeoxyguanosine DNA adduct, but did reduce photoreceptor cell apoptosis. Although the mechanism of action underlying this retinoprotection remains to be clarified, NAM may be a potential therapeutic agent for the treatment of retinal degeneration.


Dietary advice and oral nutritional supplements do not increase survival in older malnourished adults: a multicentre randomised controlled trial.
Objectives: The study aimed to investigate the effect on survival after 6 months of treatment involving individual dietary advice and oral nutritional supplements in older malnourished adults after discharge from hospital.Methods: This multicentre randomised controlled trial included 671 patients aged 65 years who were malnourished or at risk of malnutrition when admitted to hospital between 2010 and 2014, and followed up after 8.2 years (median 4.1 years). Patients were randomised to receive dietary advice or oral nutritional supplements, separate or in combination, or routine care. The intervention started at discharge from the hospital and continued for 6 months, with survival being the main outcome measure.Results: During the follow-up period 398 (59.3%) participants died. At follow-up, the survival rates were 36.9% for dietary advice, 42.4% for oral nutritional supplements, 40.2% for dietary advice combined with oral nutritional supplements, and 43.3% for the control group (log-rank test p = 0.762). After stratifying the participants according to nutritional status, survival still did not differ significantly between the treatment arms (log-rank test p = 0.480 and p = 0.298 for the 506 participants at risk of malnutrition and the 165 malnourished participants, respectively).Conclusions: Oral nutritional supplements with or without dietary advice, or dietary advice alone, do not improve the survival of malnourished older adults. These results do not support the routine use of supplements in older malnourished adults, provided that survival is the aim of the treatment.Trial registration: ClinicalTrials.gov with ID: NCT01057914.


Regional economic integration via detection of circular flow in international value-added network.
Global value chains are formed through value-added trade, and some regions promote economic integration by concluding regional trade agreements to promote these chains. However, it has not been established to quantitatively assess the scope and extent of economic integration involving various sectors in multiple countries. In this study, we used the World Input-Output Database to create a cross-border sector-wise network of trade in value-added (international value-added network) covering the period of 2000-2014 and evaluated them using network science methods. By applying Infomap to the international value-added network, we confirmed two regional communities: Europe and the Pacific Rim. We applied Helmholtz-Hodge decomposition to the value-added flows within the region into potential and circular flows, and clarified the annual evolution of the potential and circular relationships between countries and sectors. The circular flow component of the decomposition was used to define an economic integration index. Findings confirmed that the degree of economic integration in Europe declined sharply after the economic crisis in 2009 to a level lower than that in the Pacific Rim. The European economic integration index recovered in 2011 but again fell below that of the Pacific Rim in 2013. Moreover, sectoral economic integration indices suggest what Europe depends on Russia in natural resources makes the European economic integration index unstable. On the other hand, the indices of the Pacific Rim suggest the steady economic integration index of the Pacific Rim captures the stable global value chains from natural resources to construction and manufactures of motor vehicles and high-tech products.


Nucleation of gas hydrates within constant energy systems.
The early stage of formation of gas hydrates has recently attracted attention as amorphous intermediate gas hydrate structures have been observed, apparently contrary to a classical model of nucleation and some experimental observations. To date, essentially all reported molecular simulations of the nucleation of gas hydrates have been under constant temperature conditions, which does not consider the possible impacts of heat transfer on the nucleation processes. Here we show, using constant energy molecular simulations, that the nuclei at an early stage of the hydrate formation have relatively more crystalline order in comparison with those observed in previous isothermal (NPT or NVT) work. The current work suggests a more transient role for intermediate amorphous structures during hydrate nucleation, thereby providing a stronger link between molecular simulation and experimental observations. Our NVE results nevertheless support the two-step nucleation mechanism proposed in previous simulation studies under constant temperature conditions which features the initial formation of amorphous hydrate-like structures.


Rapid distinction of intracellular and extracellular proteins using NMR diffusion measurements.
In-cell NMR spectroscopy offers a unique opportunity to begin to investigate the structures, dynamics, and interactions of molecules within their functional environments. An essential aspect of this technique is to define whether observed signals are attributable to intracellular species rather than to components of the extracellular medium. We report here the results of NMR measurements of the diffusion behavior of proteins expressed within bacterial cells, and find that these experiments provide a rapid and nondestructive probe of localization within cells and can be used to determine the size of the confining compartment. We show that diffusion can also be exploited as an editing method to eliminate extracellular species from high-resolution multidimensional spectra, and should be applicable to a wide range of problems. This approach is demonstrated here for a number of protein systems, using both (15)N and (13)C (methyl-TROSY) based acquisition.


Pitavastatin and HDL: Effects on plasma levels and function(s).
Low high density lipoprotein cholesterol (HDL-C) levels represent an independent risk factor for cardiovascular disease; in addition to the reduced HDL-C levels commonly observed in patients at cardiovascular risk, the presence of dysfunctional HDL, i.e. HDL with reduced atheroprotective properties, has been reported. Despite the established inverse correlation between HDL-C levels and cardiovascular risk, several clinical trials with HDL-C-increasing drugs (such as niacin, CETP inhibitors or fibrate) failed to demonstrate that a significant rise in HDL-C levels translate into a cardiovascular benefit. Statins, that are the most used lipid-lowering drugs, can also increase HDL-C levels, although this effect is highly variable among studies and statins; the most recent developed statin, pitavastatin, beside its role as LDL-C-lowering agent, increases HDL-C levels at a significantly higher extent and progressively upon treatment; such increase was observed also when patients where shifted from another statin to pitavastatin. The stratification by baseline HDL-C levels revealed that only pitavastatin significantly increased HDL-C levels in patients with baseline HDL-C ≤45 mg/dl, while no changes were observed in patients with higher baseline HDL-C levels. In the last years the hypothesis that functional properties of HDL may be more relevant than HDL-C levels has risen from several observations. The treatment with pitavastatin not only increased HDL-C levels, but also increased the phospholipid content of HDL, increased the HDL efflux capacity and their anti-oxidant properties. These observations suggest that, besides its high LDL-C-lowering effect, pitavastatin also exhibits a significantly higher ability to increase HDL-C levels and may also positively affect the quality and functionality of HDL particles.


[Results of radical removal of malignant cerebral gliomas, by using computer-assisted navigation, followed by adjuvant therapy].
A retrospective cohort analysis of the results of treatment of patients with malignant gliomas was made in 2 groups, each comprising 43 patients. In Group 1, the tumors were radically removed under neuronavigation guidance ("Voyager SX"). In Group 2 where the patients were operated on by the same team of surgeons who did not employ computer-assisted navigation technologies. The results of different adjuvant therapy regimens were analyzed in patients after radical tumor removal under navigation guidance (Group 1). In its first subgroup, 24 patients with anaplastic astrocytes were postoperatively irradiated (60 Gy), followed by treatment with temodal (200 mg/m2 (mean 6 courses). In the second subgroup, 12 patients received chemoradiotherapy (temodal, 75 mg/m2 daily + irradiation), followed by courses (n=6) of temodal, 200 mg/m2). In the third subgroup, 7 patients were treated with fotemustin (200 mg/m2 (induction) + 5 cycles). The computer-assisted technologies substantially improve a postoperative outcome in patients with malignant glionas. Current chemoradiotherapy is relatively safe and prolongs a relapse-free interval with a high quality of life. Further studies call for the efficiency of different adjuvant therapy regimens after radical surgery.


Structural investigation of a uronic acid-containing polysaccharide from abalone by graded acid hydrolysis followed by PMP-HPLC-MSn and NMR analysis.
A new strategy was applied to elucidate the structure of a polysaccharide from abalone gonad (AGSP). It was hydrolyzed by 0.05 M, 0.2 M, 0.5 M, and 2.0 M TFA at 100 °C for 1 h, sequentially. Every hydrolysate was ultrafiltrated (3000 Da) to collect oligo- and monosaccharides, and the final retentate was further hydrolyzed with 2.0 M TFA at 110 °C and 121 °C for 2 h, respectively. 1-Phenyl-3-methyl-5-pyrazolone (PMP) derivatization followed by HPLC-MSn analysis was applied to detect the sugar residues in these hydrolysates, which allowed proposing their location in the polysaccharide structure. The retentate after 0.5 M TFA hydrolysis was confirmed as the polysaccharide backbone, and it was further analyzed by 1D and 2D NMR spectroscopy. Thus, the structural elucidation of AGSP was accomplished, and it has a backbone of →4)-β-GlcA(1→2)-α-Man(1→ repeating unit with Fuc, Xyl and Gal in the branch. The analytical strategy demonstrated was useful to characterize the structure of polysaccharides.


Cycling on rollers: Kreitler fan resistance at submaximal levels of effort.
The goal of this investigation was to characterize the commercially available fan unit for the KreitlerAlloy rollers at submaximal levels of effort (< or = 500 W). A single cyclist rode six times at each of three fan inlet settings (closed, half, and full open) and five fan speeds (900, 1800, 2700, 3600, and 4500 rpm). Fan power requirements were isolated by subtracting roller resistance from separate trials. Power requirements relative to fan inlet and fan speed possessed a significant interaction with the main effects for each also significant (all p < 0.001). Power increased to the cube of fan speed, regardless of inlet opening (r2 > or = 0.997). Fan resistance was virtually non existent at 900 rpm. Fan resistance then significantly increased with increasing fan speed and inlet opening. At 4500 rpm power requirements of the fan reached 269 +/- 6, 352 +/- 7, and 406 +/- 9 W with the inlet closed, half, and fully open, respectively (p < 0.001). The rear wheel-roller interaction supplied an additional 19 +/- 2 W on up to 104 +/- 4 W at the highest speed. Therefore, the fan unit increases the functionality of the rollers for a variety of training and testing environments.


Phylogenetic overdispersion in Floridian oak communities.
Closely related species that occur together in communities and experience similar environmental conditions are likely to share phenotypic traits because of the process of environmental filtering. At the same time, species that are too similar are unlikely to co-occur because of competitive exclusion. In an effort to explain the coexistence of 17 oak species within forest communities in North Central Florida, we examined correlations between the phylogenetic relatedness of oak species, their degree of co-occurrence within communities and niche overlap across environmental gradients, and their similarity in ecophysiological and life-history traits. We show that the oaks are phylogenetically overdispersed because co-occurring species are more distantly related than expected by chance, and oaks within the same clade show less niche overlap than expected. Hence, communities are more likely to include members of both the red oak and the white + live oak clades than only members of one clade. This pattern of phylogenetic overdispersion arises because traits important for habitat specialization show evolutionary convergence. We hypothesize further that certain conserved traits permit coexistence of distantly related congeners. These results provide an explanation for how oak diversity is maintained at the community level in North Central Florida.


The effects of early combined training on the physical development of preterm infants with different gestational ages.
To investigate the effects of early combined training on the physical development of preterm infants of different gestational ages. A total of 144 preterm infants from our hospital's neonatal intensive care unit (NICU) between 2019 and 2020 were selected as the research participants and randomly divided into an intervention group (77 cases) and a control group (67 cases). The physical development and catch-up growth satisfaction rate of preterm infants in the intervention and control groups were compared at 40 weeks, 3 months, 6 months and 12 months of corrected age. At 40 weeks of gestational age and corrected 3 months of gestational age, the physical growth indexes of the intervention group were higher than those of the control group, with a statistical difference (P < 0.05). At the corrected age of 12 months, the body weight and length of preterm infants in the <29 weeks intervention group were still higher than those in the control group (P < 0.05). The body weight of preterm infants in the 29-32 weeks and 32-34 weeks intervention groups was higher than in the control group (P < 0.05). There was no statistical difference between the intervention and control groups in the 34-37 weeks category (P > 0.05). The catch-up growth satisfaction rates of all the physical growth indexes in the intervention group were higher than those of the control group at the corrected 3 months for all the gestational ages (P < 0.05). While those indexes in the three >29 weeks intervention groups were higher than those in the <29 weeks intervention group at the corrected age of 12 months (P < 0.05). Early combined training can promote the early catch-up growth of preterm infants, especially in the early gestational age groups (<34 weeks), and the catch-up growth promotion can last for 12 months. The older the gestational age, the sooner catch-up growth satisfaction will occur.


Presynaptic and postsynaptic effects of local cathodal DC polarization within the spinal cord in anaesthetized animal preparations.
Trans-spinal DC stimulation affects both postsynaptic neurons and the presynaptic axons providing input to these neurons. In the present study, we show that intraspinally applied cathodal current replicates the effects of trans-spinal direct current stimulation in deeply anaesthetized animals and affects spinal neurons both during the actual current application and during a post-polarization period. Presynaptic effects of local cathodal polarization were expressed in an increase in the excitability of skin afferents (in the dorsal horn) and group Ia afferents (in motor nuclei), both during and at least 30 min after DC application. However, although the postsynaptic facilitation (i.e. more effective) activation of motoneurons by stimuli applied in a motor nucleus was very potent during local DC application, it was only negligible once DC was discontinued. The results suggest that the prolonged effects of cathodal polarization are primarily associated with changes in synaptic transmission. The present study aimed to compare presynaptic and postsynaptic actions of direct current polarization in the spinal cord, focusing on DC effects on primary afferents and motoneurons. To reduce the directly affected spinal cord region, a weak polarizing direct current (0.1-0.3 μA) was applied locally in deeply anaesthetized cats and rats; within the hindlimb motor nuclei in the caudal lumbar segments, or in the dorsal horn within the terminal projection area of low threshold skin afferents. Changes in the excitability of primary afferents activated by intraspinal stimuli (20-50 μA) were estimated using increases or decreases in compound action potentials recorded from the dorsal roots or peripheral nerves as their measure. Changes in the postsynaptic actions of the afferents were assessed from intracellularly recorded monosynaptic EPSPs in hindlimb motoneurons and monosynaptic extracellular field potentials (evoked by group Ia afferents in motor nuclei, or by low threshold cutaneous afferents in the dorsal horn). The excitability of motoneurons activated by intraspinal stimuli was assessed using intracellular records or motoneuronal discharges recorded from a ventral root or a muscle nerve. Cathodal polarization was found to affect motoneurons and afferents providing input to them to a different extent. The excitability of both was markedly increased during DC application, although post-polarization facilitation was found to involve presynaptic afferents and some of their postsynaptic actions, but only negligibly motoneurons themselves. Taken together, these results indicate that long-lasting post-polarization facilitation of spinal activity induced by locally applied cathodal current primarily reflects the facilitation of synaptic transmission.


Selective birth in a case of twins discordant for Tay Sachs disease.
The authors have performed selective birth in two twin pregnancies in the same patient. The couple's first pregnancy resulted in the birth of a male with Tay Sachs disease: their Pergonal-induced second pregnancy was a twin gestation discordant for Tay Sachs disease. A fetal intracardiac puncture, exsanguination, and fetal intracardiac air embolization were then performed. The patient went into premature labor 9 days later and delivered a normal immature infant, who died, and the macerated cotwin. The third Pergonal-induced pregnancy was a singleton with Tay Sachs disease and the pregnancy was terminated. Their fourth Pergonal-induced pregnancy was a twin gestation discordant for Tay Sachs disease. At 20 weeks gestation, fetal intracardiac air embolization was performed with immediate demise of the affected fetus. The pregnancy was followed closely with ultrasonography and coagulation studies and proceeded to term without complication. A normal female and a fetus papyraceous were delivered by cesarean section.


Fcc-bcc transition for Yukawa interactions determined by applied strain deformation.
Calculations of the work required to transform between bcc and fcc phases yield a high-precision bcc-fcc transition line for monodisperse point Yukawa (screened-Coulomb) systems. Our results agree qualitatively but not quantitatively with recently published simulations and phenomenological criteria for the bcc-fcc transition. In particular, the bcc-fcc-fluid triple point lies at a higher inverse screening length than previously reported.


Parent-child interaction therapy for preschool children with disruptive behaviour problems in the Netherlands.
Persistent high levels of aggressive, oppositional and impulsive behaviours, in the early lives of children, are significant risk factors for adolescent and adult antisocial behaviour and criminal activity. If the disruptive behavioural problems of young children could be prevented or significantly reduced at an early age, the trajectory of these behavioural problems leading to adolescent delinquency and adult antisocial behaviour could be corrected. Parent-Child Interaction Therapy (PCIT) is a short-term, evidence-based, training intervention for parents dealing with preschool children, who exhibit behavioural problems. Recently, PCIT was implemented in a Dutch community mental health setting. This present study aims to examine the short-term effects of PCIT on reducing the frequency of disruptive behaviour in young children. This study is based on the data of 37 referred families. Whereby the results of which are derived from an analysis of parent reports of the Eyberg Child Behavior Inventory (ECBI), obtained during each therapeutic session. Furthermore, demographic information, extracted from client files, was also utilized. However, it must be noted that eleven families (27.5%) dropped out of treatment before the treatment protocol was completed. To investigate the development of disruptive behaviour, a non-clinical comparison group was recruited from primary schools (N = 59). The results of this study indicate that PCIT significantly reduces disruptive behaviour in children. Large effect sizes were found for both fathers and mothers reported problems (d = 1.88, d = 1.99, respectively), which is similar to American outcome studies. At post treatment, no differences were found concerning the frequency of behavioural problems of children who completed treatment and those who participated in the non-clinical comparison group. The findings of this study suggest that PCIT is potentially an effective intervention strategy for young children and their parents in the Dutch population. However, further research into the evaluation of PCIT using a randomised controlled trial is recommendable.


The Differential Antitumor Activity of 5-Aza-2'-deoxycytidine in Prostate Cancer DU145, 22RV1, and LNCaP Cells.
DNA methylation is a DNA methyltransferase-mediated epigenetic modification affecting gene expression. This process is involved in the initiation and development of malignant disease. 5-Aza-2'-deoxycytidine (5-Aza), a classic DNA methyltransferase inhibitor, possesses antitumor proliferation activity. However, whether 5-Aza induces cytotoxicity in solid tumors warrants further investigated. In this study, human prostate cancer (CaP) cells were treated with 5-Aza and subjected to cell viability and cytotoxicity analysis. Reverse transcription-polymerase chain reaction and methylation-specific polymerase chain reaction assay were utilized to test the gene expression and methylation status of the p53 and p21 gene promoters. The results showed that 5-Aza differentially inhibited spontaneous proliferation, arrested the cell cycle at S phase in DU145, at G1 phase in 22RV1 and LNCaP cells, and G2 phase in normal RWPE-1 cells, as well as induced the expression of phospho-H2A.X and tumor suppressive mammary serine protease inhibitor (maspin) in all three types of CaP cells. 5-Aza also increased p53 and p21 transcription through promoter demethylation, and decreased the expression of oncogene c-Myc in 22RV1 and LNCaP cells. Western blotting analysis showed that the poly (ADP-ribose) polymerase cleavage was detected in DU145 and 22RV1 cells. Moreover, there were no significant changes in p53, p21 and c-Myc expression in DU145 cells following treatment with 5-Aza. Thus, in responsible for its apoptotic induction and DNA damage, the mechanism of the antitumor activities of 5-Aza may involve in an increase of tumor suppressive maspin, upregulation of wild type p53-mediated p21 expression and a decrease of oncogene c-Myc level in 22RV1 and LNCaP cells, and enhancing the tumor suppressive maspin expression in DU145 cells. These results enriched our understanding of the multifaceted antitumor activity of 5-Aza, and provided the expression basis of biomarkers for its possible clinical application in prostate cancer.


Magnifying chromoendoscopy of the esophagus: in-vivo pathological diagnosis using an endocytoscopy system.
The aim of the present study was to observe the endoscopic characteristics of cells on the surface layer of superficial esophageal carcinomas in vivo using an endocytoscopy system and to compare the findings with those in normal squamous epithelium. Superficial esophageal cancers in 12 patients were examined with methylene blue staining using an endocytoscopy system. The endocytoscopy system and methylene blue staining made it possible to observe cells on the surface of the squamous epithelium in normal esophageal mucosa. Normal cells were arranged homogeneously, and the nucleus cytoplasm ratio was uniform and low. In esophageal cancers, the density of cells was found to be much greater than that in normal squamous epithelium. The cell distribution was also irregular and the cells were extremely heterogeneous, with the nuclei having different staining, size, and shape characteristics. The nucleus cytoplasm ratio was also very irregular. Examining esophageal tissue using the endocytoscopy system described here makes it possible to observe detailed histological alterations in esophageal lesions in vivo.


Fcgamma-receptor IIA genotype and invasive pneumococcal infection.
Streptococcus pneumoniae is a major cause of pneumonia, bacteraemia, meningitis, and acute otitis media, especially in young children, immunocompromised patients, and elderly. Fcgamma-IIA receptor plays a crucial role in the phagocytosis of IgG2-opsonized bacteria since it is the sole receptor able to interact with IgG2 antibodies. Fcgamma-RIIA exhibits allelic polymorphisms with different capacities for binding IgG2 and phagocytosis. In a prospective study, we genotyped Fcgamma-RIIA in 55 Caucasian patients suffering from invasive pneumococcal disease and in 100 Caucasian controls. In contrast to previous reports, we found no association between Fcgamma-RIIA genotype and invasive pneumococcal disease.


Predictive Model for the Non-Invasive Diagnosis of Endometriosis Based on Clinical Parameters.
Are other pain symptoms in addition to dysmenorrhea, dyspareunia, dyschezia, dysuria, and chronic pelvic pain correlated to endometriosis and suitable for a clinical prediction model? We conducted a prospective study from 2016 to 2022, including a total of 269 women with numerous pain symptoms and other parameters. All women filled out two questionnaires and were examined by palpation and transvaginal ultrasound (TVUS). In cases of suspected deep endometriosis, magnetic resonance imaging (MRI) was performed. After the operation, endometriosis was diagnosed by histological examination. All in all, 30 significant parameters and 6 significant numeric rating scale (NRS) scores associated with endometriosis could be identified: 7 pain adjectives, 8 endometriosis-associated pain symptoms, 5 pain localizations, 6 parameters from the PainDETECT, consumption of analgesics, and allergies. Furthermore, longer pain duration (before, during, and after menstruation) was observed in women with endometriosis compared to women without endometriosis (34.0% vs. 12.3%, respectively). Although no specific pain for endometriosis could be identified for all women, a subgroup with endometriosis reported radiating pain to the thighs/legs in contrast to a lower number of women without endometriosis (33.9% vs. 15.2%, respectively). Furthermore, a subgroup of women with endometriosis suffered from dysuria compared to patients without endometriosis (32.2% vs. 4.3%, respectively). Remarkably, the numbers of significant parameters were significantly higher in women with endometriosis compared to women without endometriosis (14.10 ± 4.2 vs. 7.75 ± 5.8, respectively). A decision tree was developed, resulting in 0.904 sensitivity, 0.750 specificity, 0.874 positive predictive values (PPV), 0.802 negative predictive values (NPV), 28.235 odds ratio (OR), and 4.423 relative risks (RR). The PPV of 0.874 is comparable to the positive prediction of endometriosis by the clinicians of 0.86 (177/205). The presented predictive model will enable a non-invasive diagnosis of endometriosis and can also be used by both patients and clinicians for surveillance of the disease before and after surgery. In cases of positivety, as evaluated by the questionnaire, patients can then seek advice again. Similarly, patients without an operation but with medical therapy can be monitored with the questionnaire.


Ovarian cancer antigen CA 125 influences adhesion of human and mammalian cell lines in vitro.
Despite the widespread use of CA 125 for diagnostic and therapeutic evaluation of ovarian cancer function, the molecular nature of CA 125 is only poorly understood. It has been shown that CA 125 enhances the invasiveness of a benign endometriotic cell line in vitro. The invasiveness of cells is controlled by proteolytic activity, cell motility and cell adhesion. Therefore, we determined the influence of CA 125 on the cell adhesion of human carcinoma cell lines in vitro. In all tested human and mammalian cell lines (HECIA, AN3-CA, RL95-2, SK-OV-3, OAW-42, PA-1, HeLa, MCF7, T-47D, A-673, RT112, EJ28, EEC 145, CHO, MDBK, MDCK. LLC-PK1) the cell adhesion in vitro was significantly impaired by CA 125 in a time-dependent manner. Treatment of cells with trypsin diminished the effect of CA 125 on cell adhesion for two hours. By inhibition of protein synthesis with cycloheximide (2 microg/ml) the influence of trypsin on the anti-adhesive effect of CA 125 was significantly prolonged. The results suggest that the ovarian cancer antigen CA 125 influences cell adhesion in vitro.


Inhibition of Fc epsilon RI-mediated activation of mast cells by 2,3,4-trihydropyrimidino[2,1-a]isoquinolines.
Assays based on reporter gene technology represent today an important tool in the pharmaceutical industry for discovering novel compound classes interfering with the activation and signaling of target cells after stimulation. Here we describe a reporter gene assay targeting mast cell activation of IgE plus antigen, established in an attempt to identify substances preventing type I allergy (allergic rhinitis, allergic conjunctivitis, allergic asthma, and acute and chronic urticaria). The assay is based on a murine mast cell line designated CPII, stimulation by IgE plus antigen, and a reporter gene construct with the TNF alpha promoter linked to luciferase as a read-out system. Via screening about 50,000 substances, compound 2 was found to inhibit the reporter gene induction in the submicromolar range in this assay. Analogues of compound 2 of the 2,3,4-trihydropyrimidino[2,1-a]isoquinoline type were synthesized starting from 2-alkyl-substituted benzonitriles via aminolysis with 1,3-diaminopropane, dimetalation of 2-substituted 2-phenyl-1,4,5,6-tetrahydropyrimidines with n- and sec-butylithium, reaction with carboxylic acid methyl esters, and finally acidic dehydration. From about 50 derivatives, compound 41 was selected as a lead structure with an IC50 of 0.2 microM and a TC50 of 2.7 microM. In a first profiling in secondary assays, it effectively interfered with the production of mediators such as TNF alpha, IL-4, IL-6, IL-13, and leukotriene synthesis as measured by the corresponding ELISAs. In addition, a passive cutaneous anaphylaxis in mice (a typical type I reaction) is inhibited to more than 90% by compound 41, when administered intradermally 90 min before challenge.


Effect of metoprolol and pindolol monotherapy on plasma lipid- and lipoprotein-cholesterol levels (including the HDL subclasses) in mild hypertensive males and females.
Forty-five patients with mild hypertension were treated for 2 months with either metoprolol or pindolol in a randomized, blind, crossover study. The effects of metoprolol (100-300 mg/day) and pindolol (5-15 mg/day) on triglyceride (TG), cholesterol (C), high-density lipoprotein cholesterol (HDL-C), and HDL subfraction (HDL2-C and HDL3-C) levels were compared in males and females separately. Pindolol and metoprolol significantly elevated (10% above baseline level) the plasma TG level in both males and females. After metoprolol treatment, the HDL-C level remained unchanged in both sexes; however, a shift was found between HDL2-C and HDL3-C:HDL2-C decreased and a concomitant elevation in HDL3-C was observed. Pindolol significantly decreased total C, HDL-C, and HDL2-C levels in males. A similar trend (although the changes were not significant) was found in females. The results demonstrate the role of beta blockers in the inhibition of TG-rich lipoprotein elimination. These findings suggest that during long-term administration of metoprolol and pindolol, risks and benefits from beta-blocker therapy must be carefully considered. Continuous monitoring of lipid profiles is suggested during this treatment in order to avoid the potential worsening effect of beta blockers on risk factors of ischemic heart disease.


Body mass index and waist circumference correlate to the same degree with insulin-mediated glucose uptake.
To compare the relationship between insulin-mediated glucose uptake (IMGU) and excess adiposity as determined by measurement of either body mass index (BMI) or waist circumference (WC), IMGU was quantified by determining the steady-state plasma glucose (SSPG) concentration with the insulin suppression test and the relationship between the SSPG concentration and BMI or WC evaluated in a study of 208 healthy individuals (128 women/80 men). The results indicated that BMI and WC were correlated (P < .001) to a similar degree in both men (r = 0.90) and women (r = 0.86). Steady-state plasma glucose and both indices of excess adiposity were also significantly correlated (P < .001) to an essentially identical extent in men (r values of 0.71 vs 0.70) and women (r values of 0.54 vs 0.53). When the population was divided into tertiles on the basis of SSPG concentrations, 96% of those in the most insulin-resistant tertile were identified as being overweight/obese by BMI criteria and 84% as abdominally obese by WC criteria. However, a substantial number of those in the most insulin-sensitive tertile also demonstrated excess adiposity as defined by either BMI (45%) or WC (33%). To summarize, (1) BMI and WC correlate closely within an individual and equally well with IMGU, and (2) BMI is as effective as WC in identifying insulin-resistant individuals.


Hepatoprotective and antioxidant effects of saponarin, isolated from Gypsophila trichotoma Wend. on paracetamol-induced liver damage in rats.
The hepatoprotective potential of saponarin, isolated from Gypsophila trichotoma, was evaluated in vitro/in vivo using a hepatotoxicity model of paracetamol-induced liver injury. In freshly isolated rat hepatocytes, paracetamol (100 μ mol) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH, and elevated MDA quantity. Saponarin (60-0.006 μ g/mL) preincubation, however, significantly ameliorated paracetamol-induced hepatotoxicity in a concentration-dependent manner. The beneficial effect of saponarin was also observed in vivo. Rats were challenged with paracetamol alone (600 mg/kg, i.p.) and after 7-day pretreatment with saponarin (80 mg/kg, oral gavage). Paracetamol toxicity was evidenced by increase in MDA quantity and decrease in cell GSH levels and antioxidant defence system. No changes in phase I enzyme activities of AH and EMND and cytochrome P 450 quantity were detected. Saponarin pretreatment resulted in significant increase in cell antioxidant defence system and GSH levels and decrease in lipid peroxidation. The biochemical changes are in good correlation with the histopathological data. Protective activity of saponarin was similar to the activity of positive control silymarin. On the basis of these results, it can be concluded that saponarin exerts antioxidant and hepatoprotective activity against paracetamol liver injury in vitro/in vivo.


The use of different tobacco and related products, with and without flavours, among 15-year-olds in Slovenia.
Different tobacco and related products, like waterpipe, e-cigarettes, are gaining popularity among adolescents in different countries; the data for Slovenia is currently limited. The purpose of this paper is to present the latest data on the use of different tobacco and related products, with or without flavours, among 15-year old students in Slovenia. Data for 15-year-old students were drawn from 2014 Slovene database of the cross-national survey Health Behaviour in School-Aged Children. The survey sample was selected with stratified two-stage sampling method. The survey was performed in schools with a self-administered web questionnaire. The survey questionnaire included international compulsory, selected optional and national questions, all on a variety of topics related to youth health behaviour. 25.2% of 15-year-old students reported current (past 30-day) use of any tobacco related product, mainly cigarettes (93.1% of users), followed by waterpipe (11.7%) and cigars, cigarillos and pipes (9.4%). Exclusive use of unconventional products is low (5.1% of users). 85.5% of users of any product used one product, 48.5% of users used products with flavours. The use of different products, one or more products, and flavoured products was related to gender. A comprehensive tobacco control and prevention must address all tobacco and related products.


[Element Analysis of a Chinese Yagen Bearing the Inscription of "Product of the Ming-Zhengde Period" [Property of the Naito Memorial Museum of Pharmaceutical Science and Industry, Gifu] using an X-ray Fluorescence Spectrometer].
Yagen (see text) is an oriental grinder for crude plant medicines. It consists of a disk and navicular mortar. A Chinese yagen with the inscription, "Product of the Ming-Zhengde Period (See text), (1506-1521 A.D.)" has been housed for 40 years in the Naito Memorial Museum of Pharmaceutical Science and Industry (Kakamigahara, Gifu Prefecture, Japan). To identify the district that produced this yagen, the authors analyzed the elements using an X-ray fluorescence spectrometer. The results showed that the blue design and blue Chinese characters on the yagen were enameled with elements of cobalt, manganese, and iron. Therefore, it is believed that the yagen was made in an old porcelain kiln near Zhangzhou in Fujian Province, China. However, as the period of production could not determined in the present study, further research is needed in the future.


Genome analysis of E. coli isolated from Crohn's disease patients.
Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related. We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons. Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols.


Extended middle fossa approach for resection of a petroclival meningioma and vestibular schwannoma.
A 69-year-old woman with refractory left facial pain and subtle left hearing decline had a 13.0 × 8.1-mm left petrous apex/Meckel's cave meningioma and an 8.8 × 5.6-mm left intracanalicular vestibular schwannoma. She was otherwise neurologically intact. The anterior petrous and middle fossa approaches provide ideal access to these lesions individually, so an extended middle fossa approach was used to resect both in the same setting. She was neurologically stable postoperatively, except for a transient abducens palsy. Hearing was preserved on audiogram, and 4-month MRI displayed no tumors. The extended middle fossa approach provides excellent exposure of the petrous apex and internal auditory canal. The video can be found here: https://stream.cadmore.media/r10.3171/2022.1.FOCVID21258.


Expression of the Group A Streptococcus Fibrinogen-Binding Protein Mrp Is Negatively Regulated by the Small Regulatory RNA FasX.
The group A Streptococcus (GAS; Streptococcus pyogenes) causes an elaborate array of human diseases. In part, such variability in disease potential is a consequence of GAS manipulating the expression of a catalogue of virulence factors, with regulation occurring at both the transcriptional and posttranscriptional levels. The GAS small regulatory RNA (sRNA) FasX contributes to this regulatory activity, enhancing expression of the thrombolytic agent streptokinase, and reducing expression of collagen (pili) and fibronectin (PrtF1 and PrtF2) -binding adhesins. Here, we expand insight into the regulatory targets of FasX by identifying the M-related protein (Mrp), a fibrinogen-binding adhesin with anti-phagocytic activity, as a negatively-regulated target of FasX. Importantly, investigation of the consequences of FasX-mediated regulation led to the discovery that FasX is a major positive regulator of GAS survival and proliferation in non-immune whole human blood, with a 30-fold difference in GAS cell numbers between a fasX mutant strain and isogenic parental and complemented mutant strains. No difference in cell numbers were observed when these strains were grown in human serum, consistent with the protective phenotype associated with FasX occurring due to the inhibition of cell (e.g., neutrophil) - mediated GAS killing. The FasX-regulated factor/s responsible for the blood survival phenotype remain to be defined. In summary, we expand the known FasX regulon and identify a new phenotype associated with the regulatory activity of this key GAS sRNA. IMPORTANCE Small regulatory RNAs (sRNAs) represent a major class of regulatory molecule that promotes the ability of the group A Streptococcus (GAS) and other pathogens to regulate virulence factor expression. Despite FasX being the best-described sRNA in GAS, there remains much to be learned. Here, we highlight the importance of FasX, identifying for the first time that the loss of this sRNA results in a major reduction in the ability of GAS to survive in human blood, a phenotype critical to the ability of this human-specific pathogen to cause severe invasive infections. We also identified a novel regulatory target of FasX, thereby expanding the known regulon of this key sRNA.


Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma.
The PSMB8 and PSMB9 immunoproteasome genes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) in PSMB9 and PSMB8. We determined any associations between these SNPs and susceptibility to UBC in the Saudi community. Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for the PSMB9 rs17587 G>A and PSMB8 rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model. The PSMB9 rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21, P < 0.0001). In contrast, the PSMB8 rs2071543 SNP showed no association with UBC risk (OR = 1.13, P = 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1; P = 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4; P = 0.0026) models. Genotypic distribution of the PSMB8 rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models (P > 0.05). These results suggest a potential role for PSMB9 as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk.


BMP2 and GDF5 for Compartmentalized Regeneration of the Scapholunate Ligament.
Background Chronic injuries to the scapholunate ligament (SLIL) alter carpal kinematics and may progress to early degenerative osteoarthritis. To date, there is no consensus for the best method for SLIL reconstruction. This study aims to assess the use of growth factors (bone morphogenetic protein [BMP]2 and growth and differentiation factor 5 [GDF5]) for compartmentalized regeneration of bone and ligament in this multiphasic scaffold in a rabbit knee model. Case Description A total of 100 µg of BMP2 and 30 µg of GDF5 were encapsulated into a heparinized gelatin-hyaluronic acid hydrogel and loaded into the appropriate compartment of the multiphasic scaffold. The multiphasic scaffold was implanted to replace the native rabbit medial collateral ligament ( n = 16). The rabbits were randomly assigned to two different treatment groups. The first group was immobilized postoperatively with the knee pinned in flexion with K-wires for 4 weeks ( n = 8) prior to sacrifice. The second group was immobilized for 4 weeks, had the K-wires removed followed by a further 4 weeks of mobilization prior to sample harvesting. Literature Review Heterotopic ossification as early as 4 weeks was noted on gross dissection and confirmed by microcomputed tomography and histological staining. This analysis revealed formation of a bony bridge located within and over the ligament compartment in the intra-articular region. Biomechanical testing showed increased ultimate force of the ligament compartment at 4 weeks postimplantation consistent with the presence of bone formation and higher numbers of scaffold failures at the bone-tendon junction. This study has demonstrated that the addition of BMP2 and GDF5 in the bone-ligament-bone (BLB) scaffold resulted in heterotopic bone formation and failure of the ligament compartment. Clinical Relevance The implantation of a three-dimensional-printed BLB scaffold alone demonstrated superior biomechanical and histological results, and further investigation is needed as a possible clinical reconstruction for the SLIL.


CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid.
cgi-58 (comparative gene identification-58) is a member of alpha/beta-hydrolase family of proteins. Mutations in CGI-58 are shown to be responsible for a rare genetic disorder known as Chanarin-Dorfman syndrome, characterized by an excessive accumulation of triacylglycerol in several tissues and ichthyosis. We have earlier reported that YLR099c encoding Ict1p in Saccharomyces cerevisiae can acylate lysophosphatidic acid to phosphatidic acid. Here we report that human CGI-58 is closely related to ICT1. To understand the biochemical function of cgi-58, the gene was overexpressed in Escherichia coli, and the purified recombinant protein was found to specifically acylate lysophosphatidic acid in an acyl-CoA-dependent manner. Overexpression of CGI-58 in S. cerevisiae showed an increase in the formation of phosphatidic acid resulting in an overall increase in the total phospholipids. However, the triacylglycerol level was found to be significantly reduced. In addition, the physiological significance of cgi-58 in mice white adipose tissue was studied. We found soluble lysophosphatidic acid acyltransferase activity in mouse white adipose tissue. Immunoblot analysis using anti-Ict1p antibodies followed by mass spectrometry of the immunocross-reactive protein in lipid droplets revealed its identity as cgi-58. These observations suggest the existence of an alternate cytosolic phosphatidic acid biosynthetic pathway in the white adipose tissue. Collectively, these results reveal the role of cgi-58 as an acyltransferase.


Quantum chemistry aspects of the solvent effects on 3,4-dimethyl-2,5-dihydrothiophen-1,1-dioxide pyrolysis reaction.
A theoretical density functional theory (DFT) study was employed to investigate solvent effects on a retro-cheletropic ene reaction. The use of a nonpolar solvent in this retro-ene reaction is desirable to improve the reaction rate. Interactions between 14 different solvents and the reaction mixtures (reactant and transition state) were considered using DFT solvation calculations. These results were used to determine the role of solvents on the rate constants. Theoretical calculations at the B3LYP/6-311++G(d,p) level revealed that in the presence of solvents with low polarity the reaction becomes faster, which is in accordance with experimental data. Transition state-solvent interactions were analyzed by the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis. Finally, several correlations between electron densities in bond critical points of the C-S bond and interaction energy as well as vibrational frequencies at the transition state have been investigated.


In Silico Studies of Novel Vemurafenib Derivatives as BRAF Kinase Inhibitors.
BRAF inhibitors have improved the treatment of advanced or metastatic melanoma in patients that harbor a BRAFT1799A mutation. Because of new insights into the role of aberrant glycosylation in drug resistance, we designed and studied three novel vemurafenib derivatives possessing pentose-associated aliphatic ligands-methyl-, ethyl-, and isopropyl-ketopentose moieties-as potent BRAFV600E kinase inhibitors. The geometries of these derivatives were optimized using the density functional theory method. Molecular dynamic simulations were performed to find interactions between the ligands and BRAFV600E kinase. Virtual screening was performed to assess the fate of derivatives and their systemic toxicity, genotoxicity, and carcinogenicity. The computational mapping of the studied ligand-BRAFV600E complexes indicated that the central pyrrole and pyridine rings of derivatives were located within the hydrophobic ATP-binding site of the BRAFV600E protein kinase, while the pentose ring and alkyl chains were mainly included in hydrogen bonding interactions. The isopropyl-ketopentose derivative was found to bind the BRAFV600E oncoprotein with more favorable energy interaction than vemurafenib. ADME-TOX in silico studies showed that the derivatives possessed some desirable pharmacokinetic and toxicologic properties. The present results open a new avenue to study the carbohydrate derivatives of vemurafenib as potent BRAFV600E kinase inhibitors to treat melanoma.


Effect of nonadrenal illness on adrenal function in the cat.
Adrenal function was assessed by a combined dexamethasone suppression-ACTH stimulation test in 18 healthy cats, 17 diabetic cats, and 19 sick nondiabetic cats. In all groups, plasma cortisol concentrations decreased after dexamethasone was administered and increased after ACTH was administered. There were no significant (P greater than 0.05) differences among groups in time trend changes in cortisol concentration. There was considerable variation in adrenal response between cats in each group. Diabetic cats had more variation in base-line and postdexamethasone plasma cortisol concentrations (P less than 0.05) than did other groups. In sick, nondiabetic cats, cortisol concentrations tended to be higher in cats with hyperthyroidism (P = 0.06) than in cats with other diseases.


Extractables from filter components in model solvent streams for pharmaceutical filtration processes.
Drug manufacturers use filters widely in their manufacturing processes for bioburden reduction and sterility assurance. In implementing a pharmaceutical filtration, it is essential to determine and profile the filter extractables that could be introduced into the product. There is an ongoing industry effort to explore the analysis of extractables. Toward this end, the use of complementary analytical techniques was evaluated to aid in extractables identification by determining whether the analysis of filters in the form of components, rather than entire assemblies, facilitated the profiling of extractables. The study examines filter components of 10-inch, 0.22-microm Durapore cartridge filters using Fourier transform infra-red spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR), as well as determines the non-volatile residues (NVR) and total organic carbon contents (TOC) of the extractables. The complementary techniques of high performance liquid chromatography (HPLC/UV) and liquid chromatography nuclear magnetic resonance spectroscopy (LC/NMR) were also used. The results of the tests indicated very low levels of extractables.


Carbon Dioxide Hydrogenation into Higher Hydrocarbons and Oxygenates: Thermodynamic and Kinetic Bounds and Progress with Heterogeneous and Homogeneous Catalysis.
Under specific scenarios, the catalytic hydrogenation of CO2 with renewable hydrogen is considered a suitable route for the chemical recycling of this environmentally harmful and chemically refractory molecule into added-value energy carriers and chemicals. The hydrogenation of CO2 into C1 products, such as methane and methanol, can be achieved with high selectivities towards the corresponding hydrogenation product. More challenging, however, is the selective production of high (C2+ ) hydrocarbons and oxygenates. These products are desired as energy vectors, owing to their higher volumetric energy density and compatibility with the current fuel infrastructure than C1 compounds, and as entry platform chemicals for existing value chains. The major challenge is the optimal integration of catalytic functionalities for both reductive and chain-growth steps. This Minireview summarizes the progress achieved towards the hydrogenation of CO2 to C2+ hydrocarbons and oxygenates, covering both solid and molecular catalysts and processes in the gas and liquid phases. Mechanistic aspects are discussed with emphasis on intrinsic kinetic limitations, in some cases inevitably linked to thermodynamic bounds through the concomitant reverse water-gas-shift reaction, which should be considered in the development of advanced catalysts and processes.


[Magnetic resonance arteriography in peripheral vascular surgery. A new, non-invasive method for visualization of arteries].
Based on a MEDLINE search, we present the current status of magnetic resonance arteriography (MRA) and peripheral vascular surgery. Non-enhanced MRA (TOF-MRA) is more time-consuming than is gadolinium-enhanced MRA (CE-MRA), and the gadolinium-enhanced technique seems to perform more accurately and pose fewer problems. The sensitivity and specificity of TOF-MRA are 93% (range 64-100%) and 88% (range 57-100%) respectively, and that of CE-MRA 96% (range 71-100%) and 96% (63-100%), respectively, with conventional arteriography as the gold standard. Some studies report an incidence of run-off vessels suitable for distal bypass that are visible on MRA, but invisible on conventional arteriography. Gadolinium contrast is given intravenously and is not nephrotoxic. CE-MRA is accurate, compared to conventional arteriography, has the potential to increase the limb salvage rate for selected patients, is non-invasive, and well tolerated.


Molecular diagnosis of strongyloidiasis in a population of an endemic area through nested-PCR.
This study is aimed to diagnose and analyze strongyloidiasis in a population of an endemic area of Iran using nested-PCR, coupled with parasitological methods. Screening of strongyloidiasis infected people using reliable diagnostic techniques are essential to decrease the mortality and morbidity associated with this infection. Molecular methods have been proved to be highly sensitive and specific for detection of Strongyloides stercoralis in stool samples. A total of 155 fresh single stool samples were randomly collected from residents of north and northwest of Khouzestan Province, Iran. All samples were examined by parasitological methods including formalin-ether concentration and nutrient agar plate culture, and molecular method of nested-PCR. Infections with S. stercoralis were analyzed according to demographic criteria. Based on the results of nested-PCR method 15 cases (9.7%) were strongyloidiasis positive. Nested-PCR was more sensitive than parasitological techniques on single stool sampling. Elderly was the most important population index for higher infectivity with S. stercoralis. In endemic areas of S. stercoralis, old age should be considered as one of the most important risk factors of infection, especially among the immunosuppressed individuals.


Synthetic biomedical data generation in support of In Silico Clinical Trials.
Living in the era of Big Data, one may advocate that the additional synthetic generation of data is redundant. However, to be able to truly say whether it is valid or not, one needs to focus more on the meaning and quality of data than on the quantity. In some domains, such as biomedical and translational sciences, data privacy still holds a higher importance than data sharing. This by default limits access to valuable research data. Intensive discussion, agreements, and conventions among different medical research players, as well as effective techniques and regulations for data anonymization, already made a big step toward simplification of data sharing. However, the situation with the availability of data about rare diseases or outcomes of novel treatments still requires costly and risky clinical trials and, thus, would greatly benefit from smart data generation. Clinical trials and tests on animals initiate a cyclic procedure that may involve multiple redesigns and retesting, which typically takes two or three years for medical devices and up to eight years for novel medicines, and costs between 10 and 20 million euros. The US Food and Drug Administration (FDA) acknowledges that for many novel devices, practical limitations require alternative approaches, such as computer modeling and engineering tests, to conduct large, randomized studies. In this article, we give an overview of global initiatives advocating for computer simulations in support of the 3R principles (Replacement, Reduction, and Refinement) in humane experimentation. We also present several research works that have developed methodologies of smart and comprehensive generation of synthetic biomedical data, such as virtual cohorts of patients, in support of In Silico Clinical Trials (ISCT) and discuss their common ground.


Vertical nystagmus in routine caloric testing.
Vertical nystagmus may occur in caloric testing when only horizontal is expected. We examined this occurrence in 112 normal subjects and in 339 patients with dizziness. Vertical nystagmus was found in 29 percent of normals and in 12 percent of patients with dizziness, more often with hot than cool caloric stimuli and it is always accompanied by horizontal nystagmus. The finding occurred with peripheral and central nervous system diagnoses as well as with patients whose dizziness was considered psychogenic or was undiagnosed. Maximum slow component velocity (SCV) of vertical nystagmus was usually half or less than that of the nystagmus in the horizontal lead. The SCV time profiles of the nystagmus in horizontal and vertical leads differed considerably. Possible origins of vertical nystagmus are discussed. Whatever the origin, it is clear that the finding of vertical nystagmus in routine caloric testing does not automatically denote disease of the central nervous system.


Perceptions of control and improved psychological, physical, and social functioning in postmenopausal women.
Throughout life, social messages about women's bodies put them at greater risk of specific psychological health conditions than men; yet little is known about what psychological factors can help promote mental health in older women. In this study, we examine how perceptions of control relate to perceptions of psychological health, in addition to physical health, and social functioning in a sample of postmenopausal women. Results suggest that increased perceptions of control relate to improved perceptions of health via a reduction in negative affect. Implications for promoting health and reducing gendered mental health disparities are discussed.


'Railroad switch' technique for stent-assisted coil embolization of a wide-neck bifurcation intracranial aneurysm: technical note.
Preservation of the posterior cerebral arteries during endovascular treatment of wide-neck basilar bifurcation aneurysms remains a technical challenge despite recent device innovations. We present a novel stent deployment technique, the 'railroad switch', to protect both posterior cerebral arteries during treatment of a recurrent basilar bifurcation aneurysm. Following asymmetric basilar-posterior cerebral artery stent deployment, favoring distal placement in a posterior cerebral artery, advancement of a jailed microcatheter will advance the proximal stent into the aneurysm, protecting both posterior cerebral arteries and the native basilar terminus. This novel maneuver offers interventionalists another application of commonly used intracranial stents for endovascular management of complex basilar bifurcation aneurysms.


Investigation of the effect of movement and irrigation systems on temperature in the conventional drilling of cortical bone.
We have compared the results of the external irrigation technique with those of a double irrigation technique with continuous intermittent movement. Maximum thermal measurements were made in the cortical part of 10 samples of bovine ribs during osteotomy to simulate the preparation of a surgical bed for the installation of dental implants at a depth of 10 mm. Twenty specimens were drilled for each group: external irrigation and continuous movement (control group 1, CG1); external irrigation and intermittent movement (control group 2, CG2); double irrigation and continuous movement (test group 1, TG1); and double irrigation and intermittent movement (test group 2, TG2). The double irrigation technique gave significantly better results regardless of the drilling movement used. Thermal increases between samples was 19.2% in group CG1, 10.4% in CG2, 5.4% in TG1, and 3.4% in TG2. The double irrigation technique produced a significantly smaller increase in temperature in the cortical bone during both types of drilling (p=0.001), which illustrated its greater efficiency compared with that of the external irrigation technique.


Brief floodplain inundation provides growth and survival benefits to a young-of-year fish in an intermittent river threatened by water development.
Riverine floodplains are highly productive habitats that often act as nurseries for fish but are threatened by flow regulation. The Fitzroy River in northern Australia is facing development, but uncertainty exists regarding the extent to which floodplain habitats deliver benefits to fish, particularly given the brevity of seasonal floodplain inundation. We investigated the growth rate of young-of-year bony bream (Nematalosa erebi) in main channel and ephemeral floodplain habitats using age derived from otolith daily increments. We also investigated potential mechanisms influencing growth and modelled the consequences of differential growth rate on survival. Our results revealed higher growth occurred exclusively on the floodplain and that zooplankton biomass was the best predictor of growth rate. Modelling indicated that elevated growth rate in high-growth floodplain pools (top 25th percentile) could translate into substantial increases in survivorship. The positive effect of zooplankton biomass on growth was moderated under highly turbid conditions. Temperature had a minor influence on growth, and only in floodplain habitats. Our results indicate ephemeral floodplain habitats can deliver substantial growth and survival benefits to young-of-year fish even when floodplain inundation is brief. This study highlights the need to ensure that water policy safeguards floodplain habitats due to their important ecological role.


Aerobiological modeling I: A review of predictive models.
The present work is the first of two reviews on applied modeling in the field of aerobiology. The aerobiological predictive models for pollen and fungal spores, usually defined as predictive statistical models, will, amongst other objectives, forecast airborne particles' concentration or dynamical behavior of the particles. These models can be classified into Observation Based Models (OBM), Phenological Based Models (PHM), or OTher Models (OTM). The aim of this review is to show, analyze and discuss the different predictive models used in pollen and spore aerobiological studies. The analysis was performed on published electronic scientific articles from 1998 to 2016 related to the type of model, the taxa and the modelled parameters. From a total of 503 studies, 55.5% used OBM (44.8% on pollen and 10.7% on fungal spores), 38.5% PHM (all on pollen) and 6% OTM (5.4% on pollen and 0.6% on fungal spores). OBM have been used with high frequency to forecast concentration. The most frequent model of OBM was linear regression (18.5% out of 503) on pollen and artificial neural networks (4.6%) on fungal spores. In the PHM, the principal use was to characterize the main pollen season (flowering season) based on the model of growth degree days. Finally, OTM have been used to estimate concentrations at unmonitored areas. Olea (14,5%) on pollen and Alternaria (4,8%) on fungal spores were the taxa most frequently modelled. Daily concentration was the most modelled parameter by OBM (25.2%) and season start day by PHM (35.6%). The PHM approaches include greater model diversity and use fewer independent variables than OBM. In addition, PHM show to be easier to apply than OBM; however, the wide range of criteria to define the parameters to use in PHM (e.g.: pollination start day) makes that each model is used with a lesser frequency than other models.