Do alcohol control policies have the predicted effects on consumption? An analysis of the Baltic countries and Poland 2000-2020.
Many population-based alcohol control policies are postulated to work via changes in adult alcohol per capita consumption (APC). However, since APC is usually assessed on a yearly basis, often there are not enough data to conduct interrupted time-series or other controlled analyses. The current dataset, with 21 years of observation from four countries (Estonia, Latvia, Lithuania, and Poland), had sufficient power to test for average effects and potential interactions of the World Health Organization's (WHO) three "best buys" for alcohol control: taxation increases leading to a decrease in affordability; reduced availability (via a decrease in opening hours of at least 20 %); and advertising and marketing restrictions. We postulated that the former two would have immediate effects, while the latter would have mid- to long-term effects. Linear regression analysis. Taxation increases and availability reductions in all countries were associated with an average reduction in APC of 0.83 litres (ℓ) of pure alcohol per year (95 % confidence interval: -1.21 ℓ, -0.41 ℓ) in the same year, with no significant differences between countries. Restrictions on advertising and/or marketing had no significant immediate associations with APC (average effect 0.04 ℓ per year; 95 % confidence interval: -0.65 ℓ, 0.73 ℓ). Several sensitivity analyses corroborated these main results. The WHO "best buy" alcohol control policies of taxation increases and availability restrictions worked as postulated in these four northeastern European Union countries.


Tandem Mass Tag-Based Quantitative Proteomics and Virulence Phenotype of Hemolymph-Treated Bacillus thuringiensis kurstaki Cells Reveal New Insights on Bacterial Pathogenesis in Insects.
The spore-forming bacterium Bacillus thuringiensis (Bt) of the Bacillus cereus group uses toxin-opened breaches at the insect midgut epithelium to infest the hemolymph, where it can rapidly propagate despite antimicrobial host defenses and induce host death by acute septicemia. The response of Bt to host hemolymph and the latter's role in bacterial pathogenesis is an area that needs clarification. Here, we report a proteomic analysis of the Bt kurstaki strain HD73 (Btk) hemolymph stimulon showing significant changes in 60 (34 up- and 26 downregulated) differentially accumulated proteins (DAPs). Gene ontology (GO) enrichment analysis revealed that DAPs were mainly related to glutamate metabolism, transketolase activity, and ATP-dependent transmembrane transport. KEGG analysis disclosed that DAPs were highly enriched in the biosynthesis of bacterial secondary metabolites, ansamycins. Interestingly, about 30% of all DAPs were in silico predicted as putative virulence factors. Further characterization of hemolymph effects on Btk showed enhanced autoaggregation in liquid cultures and biofilm formation in microtiter polystyrene plates. Hemolymph-exposed Btk cells were less immunogenic in mice, suggesting epitope masking of selected surface proteins. Bioassays with intrahemocoelically infected Bombyx mori larvae showed that hemolymph preexposure significantly increased Btk toxicity and reproduction within the insect (spore count per cadaver) at low inoculum doses, possibly due to 'virulence priming'. Collectively, our findings suggest that the Btk hemolymph stimulon could be partially responsible for bacterial survival and propagation within the hemolymph of infected insects, contributing to its remarkable success as an entomopathogen. All mass spectrometry data are available via ProteomeXchange with identifier PXD021830. IMPORTANCE After ingestion by a susceptible insect and damaging its midgut epithelium, the bacterium Bacillus thuringiensis (Bt) reaches the insect blood (hemolymph), where it propagates despite the host's antimicrobial defenses and induces insect death by acute septicemia. Although the hemolymph stage of the Bt toxic pathway is determinant for the infested insects' fate, the response of Bt to hemolymph and the latter's role in bacterial pathogenesis has been poorly explored. In this study, we identified the bacterial proteins differentially expressed by Bt after hemolymph exposure. We found that about 30% of hemolymph-regulated Bt proteins were potential virulence factors, including manganese superoxide dismutase, a described inhibitor of hemocyte respiratory burst. Additionally, contact with hemolymph enhanced Bt virulence phenotypes, such as cell aggregation and biofilm formation, altered bacterial immunogenicity, and increased Bt toxicity to intrahemocoelically injected insects.


Cardiac anomaly detection considering an additive noise and convolutional distortion model of heart sound recordings.
Cardiac auscultation is an essential point-of-care method used for the early diagnosis of heart diseases. Automatic analysis of heart sounds for abnormality detection is faced with the challenges of additive noise and sensor-dependent degradation. This paper aims to develop methods to address the cardiac abnormality detection problem when both of these components are present in the cardiac auscultation sound. We first mathematically analyze the effect of additive noise and convolutional distortion on short-term mel-filterbank energy-based features and a Convolutional Neural Network (CNN) layer. Based on the analysis, we propose a combination of linear and logarithmic spectrogram-image features. These 2D features are provided as input to a residual CNN network (ResNet) for heart sound abnormality detection. Experimental validation is performed first on an open-access, multiclass heart sound dataset where we analyzed the effect of additive noise by mixing lung sound noise with the recordings. In noisy conditions, the proposed method outperforms one of the best-performing methods in the literature achieving an Macc (mean of sensitivity and specificity) of 89.55% and an average F-1 score of 82.96%, respectively, when averaged over all noise levels. Next, we perform heart sound abnormality detection (binary classification) experiments on the 2016 Physionet/CinC Challenge dataset that involves noisy recordings obtained from multiple stethoscope sensors. The proposed method achieves significantly improved results compared to the conventional approaches on this dataset, in the presence of both additive noise and channel distortion, with an area under the ROC (receiver operating characteristics) curve (AUC) of 91.36%, F-1 score of 84.09%, and Macc of 85.08%. We also show that the proposed method shows the best mean accuracy across different source domains, including stethoscope and noise variability, demonstrating its effectiveness in different recording conditions. The proposed combination of linear and logarithmic features along with the ResNet classifier effectively minimizes the impact of background noise and sensor variability for classifying phonocardiogram (PCG) signals. The method thus paves the way toward developing computer-aided cardiac auscultation systems in noisy environments using low-cost stethoscopes.


Distribution of GABA, calbindin and nitric oxide synthase in the developing chick entopallium.
The distribution of GABA, calbindin and neuronal nitric oxide synthase (nNOS) was analyzed in the developing avian entopallium. The study was carried out in chick embryos from embryonic day (E)8 to hatching postnatal day (P)0, using immunohistochemical methods. At E8, GABA-positive cells were observed in pallial regions. Neither calbindin nor nNOS-immunoreactive cells were observed. At E10, the number of GABA neurons in the prospective entopallium increased and also nNOS cells were observed. Lightly stained nNOS neurons predominated over intensely stained ones. Calbindin immunoreactivity was not observed in the entopallium. At E12, the entopallial complex appeared as the pallial region displaying the highest density of GABA neurons. Also the whole entopallium displayed an intensely stained calbindin neuropil with many embedded stained cells. From E12 on, there was a decrease in the expression of nNOS. At E14-16, both GABA and calbindin-immunoreactive neurons were numerous and homogeneously distributed within the entopallium. The whole entopallium displayed a moderately stained neuropil. From E18 to P0, GABA and nNOS immunoreactivities remained similar to previous stages. At these stages, calbindin immunoreactivity within the entopallium consisted of a moderately stained central region bordered dorsally by a pale stained region. These two areas could correspond to the entopallial core and the perientopallial belt, respectively.


Rescue of silenced UCHL1 and IGFBP4 expression suppresses clonogenicity of giant cell tumor-derived stromal cells.
Giant cell tumor (GCT) of bone is a generally benign tumor with a locally aggressive behavior. Histologically, GCTs consist of multinucleated giant cells, mononuclear histiocytes and the neoplastic fibroblast-like stromal cells (GCTSC). Growing evidence exists that GCTSCs develop from mesenchymal stem cells (MSCs), but little is known about the underlying molecular mechanisms. In previous studies we observed inactivation of the ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene in primary GCTSC due to strong DNA hypermethylation, indicating that epigenetic silencing might be involved in neoplastic transformation of MSCs. Here we investigated further candidate genes and identified strong hypermethylation of the insulin-like growth factor binding protein 4 (IGFBP4) promoter, resulting in IGFBP4 downregulation in GCTs compared to MSCs. Overexpression of UCHL1 and IGFBP4 by stable transfection of GCTSC did not influence cell viability, proliferation, migration and chemosensitivity compared to parental cells. However, colony-formation was significantly decreased suggesting that rescue of UCHL1 and IFGBP4 suppresses clonogenicity of GCT stromal cells. The observation of reduced expression of the stem-cell-specific transcription factors OCT4 and SOX2 in these cell lines further supported our findings. Epigenetic silencing of UCHL1 and IGFBP4 in GCTs might thus be a crucial event during the malignant transformation of MSCs in the context of GCT development and represent promising targets for the development of new diagnostic and therapeutic strategies.


Ventricular volume in man computed from CAT scans.
A new interactive computers has been developed to measure ventricular volume from CAT scans. Testing this system on phantoms demonstrated an accuracy to within 16%. Then a series of scans of patients with obstructive hydrocephalus was analyzed using both tradional linear measures and the computer method. None of the traditional measures were directly proportional to the calculated volume. The area measure of ventricular volume correlated well with the computer-generated values. Clinical studies which attempt to quantitate ventricular volume should use a computerized or planigraphic measure.


The CTAB-DNA precipitation method: a common mini-scale preparation of template DNA from phagemids, phages or plasmids suitable for sequencing.
This report describes a common method of obtaining template DNA from phagemids, phages and plasmids. The strategy is based on the use of the cationic detergent cetyl-trimethylammonium bromide (CTAB) for DNA precipitation. By avoiding phase separation, many manipulation steps are reduced. A time-saving modification to perform double-stranded DNA sequencing directly after alkaline-denaturation is also introduced. The protocols described here allow the researcher to obtain template DNA from a variety of initial sources, thus giving reproducible sequencing results when using T7 DNA polymerase.


Deficits in luminous flux discimination by cats with lesions of the superior colliculus-pretectum.
(1) Intact cats and cats relearning or initially learning after bilateral ablation of the superior colliculus-pretectum were trained on a simple flux discrimination in a straight maze where the stimuli were either immediately side by side at the end of the runway or were separated by an opaque barrier. (2) After ablation of the superior colliculus-pretectum, each preoperatively trained cat had a significant deficit in retention of the luminous flux discrimination regardless of whether or not the stimuli were separated by a barrier or whether the correct stimulus was darker or lighter than the incorrect stimulus. (3) Under each of the different training conditions, every cat learning the flux discrimination initially after ablation of the superior colliculus-pretectum was retarded in comparison with intact cats. (4) The severity of the postoperative learning deficit correlated highly with the total extent of the lesion in the superior colliculus and pretectum.


Synergistic growth inhibition by 9-cis-retinoic acid plus trastuzumab in human hepatocellular carcinoma cells.
A malfunction of retinoid X receptor-alpha (RXRalpha) due to phosphorylation by the Ras/mitogen-activated protein kinase signaling pathway is associated with the development of hepatocellular carcinoma (HCC). The humanized anti-HER2 monoclonal antibody trastuzumab inhibits the activation of HER2 and its multiple downstream signaling pathways, including the Ras/mitogen-activated protein kinase pathway. In this study, the effects of phosphorylation of RXRalpha on the ability of RXRalpha ligand 9-cis-retinoic acid (9cRA) and trastuzumab to inhibit growth of HCC cells was examined. The effects of a combination of 9cRA plus trastuzumab on the inhibition of cell growth in HLF human HCC cells which express constitutive activation of HER2 protein were examined. The combination of 9cRA plus trastuzumab synergistically inhibited the growth of HLF cells without affecting the growth of Hc normal human hepatocytes. Combined treatment with these agents acted synergistically to induce apoptosis in HLF cells. The treatment of HLF cells with trastuzumab alone inhibited the phosphorylation of HER2, RXRalpha, ERK, Akt, and Stat3 proteins and these effects were enhanced when the cells were cotreated with 9cRA. Reporter assays indicated that the combination of 9cRA plus trastuzumab markedly increased both the retinoic acid responsive element and retinoid X responsive element promoter activities in HLF cells. 9cRA and trastuzumab cooperatively inhibit the activation of HER2 and its downstream signaling pathways, subsequently inhibiting the phosphorylation of RXRalpha and the growth of HCC cells. This combination might therefore be effective for the chemoprevention and chemotherapy of HCC.


Child with Jaundice and Pruritus: How to Evaluate?
Jaundice with pruritus is a manifestation of cholestasis. The defective biliary drainage causes accumulation of substances that are usually excreted in bile, which in turn causes pruritus. The exact nature of the pruritogen is under evaluation. However, lysophosphatidic acid is the current favourite. The causes of cholestasis can be broadly classified as intra or extrahepatic, with intrahepatic disorders being more often associated with pruritus. Cholestatic phase of acute viral hepatitis, progressive familial intrahepatic cholestasis, syndromic and non-syndromic paucity of intralobular bile ductules, drug induced cholestasis and sclerosing cholangitis (SC) are the common causes in children. An algorithmic approach facilitates early etiological diagnosis by careful clinical evaluation combined with investigations including gamma glutamyl transpeptidase, radiological imaging (ultrasonography, magnetic resonance cholangiopancreatography), liver biopsy and genetic analysis. Management is largely supportive and includes nutritional rehabilitation with supplement of fat soluble vitamins and calcium, stepwise therapy of pruritus with drugs (ursodeoxycholic acid, rifampicin, bile acid sequestrants and/or opioid antagonists) and biliary diversion surgery. Complications of advanced liver disease and portal hypertension need to be addressed. Liver transplantation is required in children with refractory pruritus affecting the quality of life or those with end stage liver disease. Relief of biliary obstruction by endoscopy or surgery and treatment of diseases associated with SC like histiocytosis may be rewarding. Long-term follow-up for development of complications of liver disease and hepatocellular/ cholangiocarcinoma is essential. Thus, an early diagnosis and stepwise treatment with an understanding of the pathogenesis of pruritus in cholestatic disorders may decrease morbidity and mortality.


Trichostrongylus colubriformis infection of guinea pigs: genetic basis for variation in susceptibility to infection among outbred animals.
Two lines of guinea-pigs, whose susceptibilities to infection with the parasitic nematode Trichostrongylus colubriformis differ significantly, have been established. This difference is probably based on genetically determined differences between the ability of members of each line to bring about immune expulsion of the parasite.


Emerging Treatment Strategies for Cerebral Ischemia-Reperfusion Injury.
Cerebral ischemia-reperfusion injury (CI/RI) injury is a common feature of ischemic stroke which occurs when the blood supply is restored after a period of ischemia in the brain. Reduced blood-flow to the brain during CI/RI compromises neuronal cell health as a result of mitochondrial dysfunction, oxidative stress, cytokine production, inflammation and tissue damage. Reperfusion therapy during CI/RI can restore the blood flow to ischemic regions of brain which are not yet infarcted. The long-term goal of CI/RI therapy is to reduce stroke-related neuronal cell death, disability and mortality. A range of drug and interventional therapies have emerged that can alleviate CI/RI mediated oxidative stress, inflammation and apoptosis in the brain. Herein, we review recent studies on CI/RI interventions for which a mechanism of action has been described and the potential of these therapeutic modalities for future use in the clinic.


Drug-induced agranulocytosis: impact of different fcgamma receptor polymorphisms?
Drug-induced agranulocytosis is a rare but life-threatening side effect which is possibly based on immunogenetic mechanisms. Some studies regarding agranulocytosis induced by the atypical antipsychotic clozapine dealing with HLA subtyping and enzyme polymorphisms have been performed to elucidate its genetic background. To further screen possibly genetically based pathways of developing agranulocytosis, we assessed clinically relevant polymorphisms of immunoglobulin G or Fcgamma receptors in patients with clozapine-induced (n = 48), ticlopidine-induced (n = 11), thyroid inhibitors-induced agranulocytosis (n = 8), and controls (n = 75). We found significant age-related effects in each of the drug-induced agranulocytoses but no further associations that underline an effect of polymorphisms in FcgammaRIIa, FcgammaRIIIa, and FcgammaRIIIb genes on drug-induced agranulocytosis. Thus, Fcgamma receptors may not serve as a genetic marker to identify patients at risk for this life-threatening side effect.


Scaffold-associated regions: cis-acting determinants of chromatin structural loops and functional domains.
It has been proposed that scaffold-associated regions are DNA elements that form the bases of chromatin loops in eukaryotic cells. Recent evidence supports a role for these elements as cis-acting 'handlers' of both structural and functional chromatin domains.


Time to grow up: the temporal role of smallRNAs in plants.
Over the past two years, several Arabidopsis genes that were initially identified as vegetative phase change mutants have been shown to have roles in smallRNA (sRNA) biogenesis. This has led to the identification of a new class of short interfering RNAs (siRNAs) called trans-acting siRNAs (ta-siRNAs).


Volumetric and Correlational Implications of Brain Parcellation Method Selection: A 3-Way Comparison in the Frontal Lobes.
The aims of this study were to compare distinct brain frontal lobe parcellation methods across 90 brain magnetic resonance imaging scans and examine their associations with cognition in older age. Three parcellation methods (Manual, FreeSurfer, and Stereology) were applied to T1-weighted magnetic resonance imaging of 90 older men, aged ∼ 73 years. A measure of general fluid intelligence (gf) associated with dorsolateral frontal regions was also derived from a contemporaneous psychological test battery. Despite highly discordant raw volumes for the same nominal regions, Manual and FreeSurfer (but not Stereology) left dorsolateral measures were significantly correlated with gf (r > 0.22), whereas orbital and inferior lateral volumes were not, consistent with the hypothesized frontal localization of gf. Individual differences in specific frontal lobe brain volumes--variously measured--show consistent associations with cognitive ability in older age. Importantly, differences in parcellation protocol for some regions that may impact the outcome of brain-cognition analyses are discussed.


Sources of variation in rapidly inducible responses to leaf damage in the mountain birch-insect herbivore system.
Studies on rapidly inducible resistance in trees against insect herbivores show substantial variation in the strength of responses. Here we report the results of a study which examined causes of this variation. We bioassayed the quality of leaves of two developmental phases (young vs. mature) of the mountain birch Betula pubescens ssp. tortuosa by measuring the growth of two instars of Epirrita autumnata larvae. We used only short shoot leaves from trees of a natural stand, uniform in size and age. Damage was caused by larvae and artificial tearing of leaf lamina, varying the scale and time. We separated seasonal changes in plants from instar-dependent effects of the animals by testing experimental larvae in two subsequent growth trials. We found that only larval-made damage induced responses in leaves that made the leaves significantly poorer quality for the test larvae. Artificial damage induced only weak responses, and artificial canopy-wide damage even caused slight improvement of leaf quality. Cumulative leaf damage did not strengthen birch responses. Leaves that were in the expansion phase responded to damage while fully-expanded, mature leaves showed no response. The pattern of responses indicated that there might be physiological constraints: small-scale damage induced resistance against the larvae but largescale damage did not. Prevalent weather conditions might have modified these responses. Larvae of two instars and sexes, of low- and high-density populations responded to leaf damage similarly. However, prior experience of larvae with the host plant may have affected subsequent larval performance. Variation in rapidly inducible responses in birches was caused by plant characters rather than by test animals.


Invasiveness of hepatocellular carcinoma cell lines: contribution of membrane-type 1 matrix metalloproteinase.
Intrahepatic metastasis is one of the malignant features of hepatocellular carcinoma (HCC). Matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (u-PA)/plasmin, are known to be associated with the invasive properties of various types of tumor cells. In this study, we examined which proteinases play a role in the metastatic invasion of human HCC cell lines. JHH-5 and JHH-6 cells constitutively expressed mRNAs for both membrane-type 1 matrix metalloproteinase (MT1-MMP) and u-PA and invaded through reconstituted MATRIGEL in vitro, whereas JHH-7 cells expressed u-PA mRNA but not MT1-MMP and did not invade. However, hepatocyte growth factor (HGF) induced MT1-MMP expression on the surface of JHH-7 cells and markedly increased invasiveness of JHH-7 in a concentration-dependent manner. Moreover, cleavage activity for pro-MMP-2 was induced in HGF-treated JHH-7 cells. MMP inhibitor, rather than serine proteinase inhibitor, potently inhibited HCC cell invasion. Intrahepatic injection of HCC cell lines into athymic nude mice caused visible intrahepatic metastases in vivo. Moreover, JHH-7 tumors showed expression of MT1-MMP mRNA, while in vitro cultured JHH-7 cells did not. These findings suggest that MT1-MMP plays an important role in the invasive properties of HCC cells, and that HGF modifies the invasive properties of noninvasive HCC cells.


[Reproducibility of goniometry with slitlamp-adapted optical coherence tomography].
Visualization of the anterior chamber angle (ACA) is an important diagnostic part of evaluating patients with glaucoma. The purpose of this study was to evaluate the intra- and interobserver variability and reliability of the ACA and angle opening distance (AOD) measurements using optical coherence tomography (OCT). To evaluate the intra- and interobserver variability, ACA and AOD were both measured five times and in three consecutive images in 22 patients (24 eyes) by two experienced observers. The intraclass correlation coefficient (ICC) as a measure of reliability was determined to estimate the intra- and interobserver variability. The main outcome measures were accuracy, reproducibility assessed with the coefficient of variation (CV), and the limits of agreement of ACA and AOD. The intraobserver variability of five replicate measurements was +/-1.4 degrees for ACA (CV 6.2%) and +/-11 micro m for AOD (CV 4%). The ICC for the intraobserver reliability was 0.99 for both ACA and AOD. The interobserver variability of three intersessional measurements was +/-2.5 degrees for ACA (CV 10.9%) and +/-24 micro m (CV 8.3%) for AOD. The ICC was 0.95 for ACA and 0.98 for AOD. There was no difference ( p>0.05) between the two observers measuring ACA and AOD. Two-dimensional visualization of the ACA and its assessment with slitlamp-adapted OCT yielded reliable ACA and AOD measurements in a clinical setting. Thus, OCT goniometry could provide an objective method to assess the anterior chamber angle.


The many faces of the SOCS box.
The suppressors of cytokine signalling (SOCS) box is a structural domain found at the C-terminus of over 70 human proteins. It is usually coupled to a protein interaction module such as an SH2 domain in case of SOCS proteins, a family of modulators of cytokine signaling. The SOCS box participates in the formation of E3 ligase complexes, marking activated cytokine receptor complexes for proteasomal degradation. A similar mechanism was recently uncovered for controlling SOCS activity itself, since SOCS2 was found to enhance the turnover of other SOCS proteins. The SOCS box can also add unique features to individual SOCS proteins: it can function as an adaptor domain as was demonstrated for SOCS3, or as a modulator of substrate binding in case of CIS. In this review we discuss these multiple roles of the SOCS box, which emerges as a versatile module controlling cytokine signaling via multiple mechanisms.


Critical factors in the development of fluorescence polarization-based peptide binding assays: an equilibrium study monitoring specific peptide binding to soluble HLA-A*0201.
There is currently a significant interest in the identification and validation of HLA-restricted CTL epitopes, which are thought to have important implications for the development of preventive and/or therapeutic applications in bacterial or viral infections, autoimmune diseases, and cancer. To better facilitate epitope discovery and validation, we present a cell- and radioisotope-free HLA-A*0201 assay system which relies upon fluorescence polarization. The assay has the advantage of allowing real-time measurements in solution without separation steps. In this report, we directed our efforts towards enhancing the sensitivity and reproducibility of the assay by conducting an in-depth analysis of parameters critical for standardization. Initial experiments demonstrated that the attachment of a fluorescence moiety at positions 5 and 8 for 9-mers and positions 5 and 6 for 10-mers, respectively, does not interfere with ligand binding to soluble HLA-A*0201. In addition, it was found that their binding to HLA-A*0201 was very effective showing high affinity binding with K(d)'s between 10.7 to 21.8 nM and binding capacities of up to 37%. In order to deliver maximized responses, factors such as the regulation of thermal HLA activation parameters to initiate peptide exchange as well as the specific adjustment of assay components were identified. Overall, the results obtained clearly demonstrate high accuracy, sensitivity and reproducibility of the FP-based assay approach. With the need for both increased throughput and miniaturized volumes, this fully homogenous, fluorescent-type binding assay is expected to be useful for routine analysis of peptide binding to MHC class I as well as class II molecules.


Current strategies and perspectives for active and passive immunization against Respiratory Syncytial Virus in childhood.
Despite the global impact of the Respiratory Syncytial Virus (RSV) infection in children, only one monoclonal antibody (Palivizumab) has been approved for clinical use. However, advances in the knowledge of RSV immunology may enable the development of safe and effective new vaccines and monoclonal antibodies in a few years. The purpose of this review is to summarize available data on approved and developing passive and active immunizations against RSV in childhood and pregnancy. A non-systematic review of RSV immunoprophylaxis in childhood and pregnancy was carried out in PubMed, path.org and clinical trial registries, without language restrictions, up to September 2022. Three monoclonal antibodies and 17 active immunization candidates are under development in phase 1 to 3 clinical studies. Regarding the first group, Nirsevimab is a monoclonal antibody with a prolonged half-life whose approval for clinical use is expected in the next months. Among the vaccines under development, six techniques are being used: protein subunit, viral particles, live attenuated virus, recombinant viral vector, chimeric, and mRNA. The first two approaches are being tested primarily in pregnancy, while the others are being developed for the pediatric population. The approval of extended half-life monoclonal antibodies is the next expected advance in RSV prevention, although the costs may be a barrier to the implementation. Regarding active immunizations, maternal and infant vaccination are complementary strategies and there are many promising candidates in clinical studies using different platforms.


Automated and combined HIV, HBV, HCV, and syphilis testing among illegal gold miners in French Guiana using a standardized dried blood device.
Blood spotted onto filter paper can be easily collected outside healthcare facilities and shipped to a central laboratory for serological testing. However, dried blood testing generally requires manual processing for pre-analytical steps. In this study, we used a standardized blood collection device combined with an automated elution system to test illegal gold miners living in French Guiana for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis. We included 378 participants, 102 females and 266 males, in three illegal gold mining resting sites. Blood collected on the Ser-Col device (Labonovum) was eluted using an automated system (SCAUT Ser-Col automation, Blok System Supply) and an automated analyzer (Alinity i, Abbott). Ser-Col results were compared to both plasma results, considered the gold standard, and to Dried blood Spot (DBS) results, considered the reference sampling method using dried blood. In plasma samples, two participants (0.5%) tested positive for HIV, six (1.5%) tested positive for hepatitis B surface antigen (HBsAg), eight were weakly positive for anti-HCV antibodies but negative for HCV RNA, and 47 tested positive for treponemal antibodies (12.4%), including 20 females (19.6%) and 27 males (9.8%, p= 0.010179). We observed a full concordance of Ser-Col and DBS results for HIV diagnosis compared to plasma results. Ser-Col and DBS samples tested positive in five HBsAg carriers and negative for one participant with a low HBsAg level in plasma (0.5 IU/mL). All participants tested negative for HCV in Ser-Col and DBS samples, including the eight participants who tested low positive for HCV antibodies and HCV RNA negative in plasma. Among syphilis seropositive participants, 41 (87.2%) and 40 (85.1%) tested positive for treponemal antibodies in Ser-Col and DBS samples, respectively. The Ser-Col method allows automated dried blood testing of HIV, HBV, HCV and syphilis with performances comparable to DBS. Automated approaches to test capillary blood transported on dried blood devices may facilitate large-scale surveys and improve testing of populations living in remote areas.


Pre-symptomatic detection of COVID-19 from smartwatch data.
Consumer wearable devices that continuously measure vital signs have been used to monitor the onset of infectious disease. Here, we show that data from consumer smartwatches can be used for the pre-symptomatic detection of coronavirus disease 2019 (COVID-19). We analysed physiological and activity data from 32 individuals infected with COVID-19, identified from a cohort of nearly 5,300 participants, and found that 26 of them (81%) had alterations in their heart rate, number of daily steps or time asleep. Of the 25 cases of COVID-19 with detected physiological alterations for which we had symptom information, 22 were detected before (or at) symptom onset, with four cases detected at least nine days earlier. Using retrospective smartwatch data, we show that 63% of the COVID-19 cases could have been detected before symptom onset in real time via a two-tiered warning system based on the occurrence of extreme elevations in resting heart rate relative to the individual baseline. Our findings suggest that activity tracking and health monitoring via consumer wearable devices may be used for the large-scale, real-time detection of respiratory infections, often pre-symptomatically.


Catheterisation: a patient perspective.
Catherisation can be a traumatic experience for some. In this comment piece, a patient discusses his experience of having a catheter in situ for 5 weeks.


The relationship between preoperative T helper cytokines in the ileal mucosa and the pathogenesis of pouchitis.
Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed. To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction. This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined. Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03). IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.


Bypass surgery versus endovascular interventions in severe or critical limb ischemia.
Critical limb ischemia is associated with a significant morbidity and mortality. We systematically reviewed the evidence to compare bypass surgery with endovascular revascularization in patients with critical limb ischemia. We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus through October 2014 for comparative studies (randomized and nonrandomized). Predefined outcomes of interest were mortality, major amputation, patency, and wound healing. We pooled odds ratios (ORs) of the outcomes of interest using the random-effects model. Nine studies that enrolled 3071 subjects were included. There was no significant difference in mortality (OR, 0.72; 95% confidence interval [CI], 0.44-1.16) or amputation (OR, 1.2; 95% CI, 0.87-1.65). Bypass surgery was associated with higher primary patency (OR, 2.50; 95% CI, 1.25-4.99) and assisted primary patency (OR, 3.39; 95% CI, 1.53-7.51). The quality of evidence was low for mortality and amputation outcomes and moderate for patency outcomes. Low quality of evidence due to imprecision and heterogeneity suggests that bypass surgery and endovascular approaches may have similar effect on mortality and major amputations. However, better primary and primary assisted patency can be expected with surgery.


Photooxidation products of primaquine. Structure, antimalarial activity and hemolytic effects.
Photooxidation of primaquine (1) and 5-hydroxyprimaquine (5) afforded a blue dye for which o-quinone structure 4 was elaborated. Similar oxidation of N-ethoxyacetylprimaquine (10) afforded o-quinone 11. Tissue schizontocidal activity of 4 and 11, and bisquinolylmethine 3 prepared earlier, showed that none of them had noteworthy antimalarial activity, but all three produced methemoglobin.


Clonidine elicits a long-term depression in mucosal red cell flux.
To evaluate the impact of clonidine on mucosal red cell flux during baseline sedation with propofol or sevoflurane, respectively. Six healthy, chronically instrumented dogs for the measurement of cardiac output (CO) were repeatedly studied. During baseline sedation with either propofol (15 mg x kg(-1) x h(-1)) or sevoflurane (1.5 MAC), local tissue cell flux was assessed using laser Doppler flowmetry at the enoral mucosa. After baseline measurements, a bolus of clonidine (2.0 microg/kg) was infused within 1 min. Data are presented as mean +/- SEM; ANOVA, Scheffé's post hoc test, p < 0.05. Clonidine significantly reduced CO from 75 +/- 4 and 75 +/- 6 ml x kg(-1) x min(-1) (sedation with propofol or sevoflurane, respectively) to 40 +/- 3 and 49 +/- 5 ml x kg(-1) x min(-1), however, with almost complete recovery to baseline after 30 min (70 +/- 4 and 71 +/- 6 ml x kg(-1) x min(-1), NS from baseline). Similarly, clonidine decreased mucosal red cell flux by 44 +/- 8% and 54 +/- 4%. However, mucosal perfusion did not return to baseline (-25 +/- 5% and -27 +/- 3%). In spite of the rapid return to baseline in systemic perfusion, the mucosal red cell flux of the enoral mucosa remained markedly reduced after a single bolus of clonidine. Given the crucial role of preserved microcirculatory perfusion for an intact mucosal barrier function, our data suggest that clonidine might impair this important mechanism to prevent the translocation of bacteria and endotoxins into the systemic circulation.


No Significant Effects of Cellphone Electromagnetic Radiation on Mice Memory or Anxiety: Some Mixed Effects on Traumatic Brain Injured Mice.
Current literature details an array of contradictory results regarding the effect of radiofrequency electromagnetic radiation (RF-EMR) on health, both in humans and in animal models. The present study was designed to ascertain the conflicting data published regarding the possible impact of cellular exposure (radiation) on male and female mice as far as spatial memory, anxiety, and general well-being is concerned. To increase the likelihood of identifying possible "subtle" effects, we chose to test it in already cognitively impaired (following mild traumatic brain injury; mTBI) mice. Exposure to cellular radiation by itself had no significant impact on anxiety levels or spatial/visual memory in mice. When examining the dual impact of mTBI and cellular radiation on anxiety, no differences were found in the anxiety-like behavior as seen at the elevated plus maze (EPM). When exposed to both mTBI and cellular radiation, our results show improvement of visual memory impairment in both female and male mice, but worsening of the spatial memory of female mice. These results do not allow for a decisive conclusion regarding the possible hazards of cellular radiation on brain function in mice, and the mTBI did not facilitate identification of subtle effects by augmenting them.


Parent-rating vs performance-based working memory measures: Association with spoken language measures in school-age children.
Working memory (WM) assessment is often part of cognitive-linguistic test batteries. The author examined the relationship between parent rating of WM functioning and children's performance-based WM, and the relationship of each with receptive and expressive spoken language measures. Study participants were eighty-three 7- to 11-year-old children. The sample represented a broad range of cognitive abilities. No participating child had frank neurological or intellectual disabilities, autism, fluency disorder, or hearing loss. Parents completed a standardized executive function rating scale that included a WM subscale. Children completed a standardized WM task and an experimental WM task. Children also completed six standardized language measures. Results showed that there was no correlation between parent rating and either of the performance-based WM tasks as well as the composite WM performance score. Parent rating of WM functioning was not related to any of the language scores whereas the composite WM performance score showed significant links with language abilities. Although parent rating and performance-based WM measures are designed to reflect the same cognitive construct, they are not correlated. Potential reasons for the findings and implications of using parent-rating and performance-based WM measures in school-age children are discussed.


Is 99m Tc bone scintigraphy necessary in the preoperative workup for patients with cT1N0 subsolid lung cancer? A prospective multicenter cohort study.
99m Tc bone scintigraphy (BS) is still the most common approach for the evaluation of bone metastasis in China. The purpose of this study was to investigate the necessity of BS as part of a routine preoperative workup for patients with cT1N0 subsolid lung cancer. This was a prospective multicenter clinical trial (NCT03689439). Patients with cT1N0 subsolid nodules who were candidates for surgical resection were consecutively enrolled into the study. BS was performed preoperatively. The surgical plan could be changed if a positive result was detected. The primary endpoint was the incidence rate of the surgical plan being changed because of positive BS results. The secondary endpoint was the rate of positive BS findings and the rate of related complications. From November 2018 to July 2019, 691 patients were enrolled into the study. None of the patients had positive BS results and no surgical plans were changed by BS findings. There were 222 male and 469 female patients. The average age was 54.8 ± 3.7 years old. The average tumor diameter was 14.9 ± 4.2 mm. There were 282 patients with pure GGO nodules and 409 with part-solid nodules. A total of 470 patients had a single nodule, while 221 patients had multifocal lesions. The number of patients whose pathological diagnosis was invasive adenocarcinoma, minimally invasive adenocarcinoma, adenocarcinoma in situ and mucinous adenocarcinoma was 357, 293, 32 and nine, respectively. The number of patients who underwent lobectomy, segmentectomy and wedge resection was 234, 199 and 258, respectively. 99m Tc bone scintigraphy is unnecessary in the preoperative workup for patients with cT1N0 subsolid lung cancer. SIGNIFICANT FINDINGS OF THE STUDY: In this prospective study of 691 patients with cT1N0 subsolid lung cancer, no surgical plans were affected by positive bone scan findings. We suggest physicians consider canceling BS from preoperative workup for cT1 subsolid lung cancer patients. Clinical trial registry number: NCT03689439.


Reserve capacity of bicarbonate secretion in chronic pancreatitis.
When secretin was given by continuous intravenous infusion in the control subjects, the dose of secretin inducing maximal bicarbonate output was found to be around 6.0 CHR U/kg/hr. Then the pancreatic exocrine secretory response to sequential standard (1.2 CHR U/kg/hr) and augmented (6.0 CHR U/kg/hr) dose of secretin was studied in the controls, in patients with chronic pancreatitis and in its suspected cases. This new method for exocrine pancreatic function did not offer advantage for the diagnosis of well established chronic pancreatitis. But from the results obtained in suspected chronic pancreatitis it was supposed that the decline of increasing rate of bicarbonate output with augmentation of dose and the decrease of response to augmented dose of secretin might be one of functional disorders occurred in the early stage of chronic pancreatitis.


Distal radial artery (Snuffbox) access for intracranial aneurysm treatment using the Woven EndoBridge (WEB) device.
Preliminary experience with distal radial artery (dRA) access for diagnostic cerebral angiography and some neurointerventional procedures has proved to be promising with good technical results and a reliable safety profile. Vascular access via the dRA may further improve minimally invasive treatment of intracranial aneurysms. Between July 2019 and June 2020 we identified 11 patients (9 females) with a mean age of 63.5 years who underwent WEB device placement for treatment of their intracranial aneurysm via the dRA approach. The mean aneurysm size (largest diameter) was 6.7 mm. One patient required conversion to femoral access due to severe brachial artery fibromuscular dysplasia. Placement of the WEB device was successful in all other cases via dRA approach. In all but one case, a low profile triaxial catheter system with the 6F Benchmark guide catheter (Penumbra) and 5F Sofia distal access catheter (Microvention) were used. No access related complications were observed. The combination of the intrasaccular WEB device and dRA access represents an ideal approach which offers operators a low risk vascular access and high procedural success by maintaining the ability to precisely place and manipulate the device using low-profile catheter systems. At the same time, this approach offers patients the most minimally invasive experience currently available for treatment of intracranial aneurysms with quick postprocedural recovery, minimal restrictions and low risk for access site complications.


Exosomal targeting and its potential clinical application.
Exosomes are extracellular vesicles secreted by a variety of living cells, which have a certain degree of natural targeting as nano-carriers. Almost all exosomes released by cells will eventually enter the blood circulation or be absorbed by other cells. Under the action of content sorting mechanism, some specific surface molecules can be expressed on the surface of exosomes, such as tetraspanins protein and integrin. To some extent, these specific surface molecules can fuse with specific cells, so that exosomes show specific cell natural targeting. In recent years, exosomes have become a drug delivery system with low immunogenicity, high biocompatibility and high efficacy. Nucleic acids, polypeptides, lipids, or small molecule drugs with therapeutic function are organically loaded into exosomes, and then transported to specific types of cells or tissues in vivo, especially tumor tissues, to achieve targeting drug delivery. The natural targeting of exosome has been found and recognized in some studies, but there are still many challenges in effective clinical treatments. The use of the natural targeting of exosomes alone is incapable of accurately transporting the goods loaded to specific sites. Besides, the natural targeting of exosomes is still an open question in disease targeting and efficient gene/chemotherapy combined therapy. Engineering transformation and modification on exosomes can optimize its natural targeting and deliver the goods to a specific location, providing wide use in clinical treatment. This review summarizes the research progress of exosomal natural targeting and transformation strategy of obtained targeting after transformation. The mechanism of natural targeting and obtained targeting after transformation are also reviewed. The potential value of exosomal targeting in clinical application is also discussed.


Negative reward expectations in Borderline Personality Disorder patients: neurophysiological evidence.
Borderline Personality Disorder (BPD) patients present profound disturbances in affect regulation and impulse control which could reflect a dysfunction in reward-related processes. The current study investigated these processes in a sample of 18 BPD patients and 18 matched healthy controls, using an event-related brain potentials methodology. Results revealed a reduction in the amplitude of the Feedback-Related Negativity of BPD patients, which is a neurophysiological index of the impact of negative feedback in reward-related tasks. This reduction, in the effect of negative feedback in BPD patients, was accompanied by a different behavioral pattern of risk choice compared to healthy participants. These findings confirm a dysfunctional reward system in BDP patients, which might compromise their capacity to build positive expectations of future rewards and decision making.


Quantitation of bentysrepinine (Y101) in rat plasma by liquid chromatography tandem mass spectrometry: application to pharmacokinetic study.
A simple, accurate and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of bentysrepinine (Y101) in rat plasma. After the addition of diphenhydramine (internal standard, IS), plasma samples were pretreated by protein precipitation. Chromatographic separation was carried out on an Atlantis(®) analytical column (4.6 mm × 100 mm, 5 μm, Waters) with methanol: 20 mM ammonium formate consisting of 1.0% formic acid (65:35, v/v) as the mobile phase at an isocratic flow rate of 0.4 mL/min for 7.5 min. The multiple reaction monitoring (MRM) transitions were performed at m/z 490.2→339.5 for Y101 and m/z 256.0→167.0 for IS on a SCIEX API 4000 mass spectrometer in the positive ion mode with electrospray ionization (ESI) source. Good linearity was achieved over the concentration range of 1-2500 ng/mL. The intra- and inter-day precisions were less than 8.3%, and the accuracy ranged from -4.0% to 2.8%. Y101 was stable during the analysis and the storage period. The pharmacokinetic profiles of Y101 at three dose levels were successfully studied for the first time in rats by this method. After single intra-gastric administration of Y101 at the doses of 25, 50 and 100 mg/kg, C(max) and AUC(0-t) were proportional to the doses given.


Knowledge and attitude toward informed consent among private dental practitioners in bathinda city, punjab, India.
A study was conducted with the purpose to assess the knowledge and attitude towards informed consent among private dental practitioners in Bathinda City, Punjab, India. A cross-sectional survey was conducted among all private dental practitioners in Bathinda City. A self-administered structured questionnaire consisting of 14 items was used to assess their knowledge and attitude regarding informed consent. The response format was based on a 3-point Likert scale. One-way analysis of variance, independent sample t test, and stepwise multiple linear regression analysis were utilized for statistical analysis. Confidence level and level of significance were set at 95% and 5%, respectively. The mean scores for knowledge and attitude were 19.37 ± 31.82 and 9.40 ± 1.72, respectively. Analysis revealed that qualification and years of experience was statistically significant among both dependent variables (p ≤ 0.05). An unbalanced knowledge of informed consent among the current dentists has suggested the need for awareness programs to fill the knowledge gaps and instill positive attitudes.


High glutathione and glutathione peroxidase-2 levels mediate cell-type-specific DNA damage protection in human induced pluripotent stem cells.
Pluripotent stem cells must strictly maintain genomic integrity to prevent transmission of mutations. In human induced pluripotent stem cells (iPSCs), we found that genome surveillance is achieved via two ways, namely, a hypersensitivity to apoptosis and a very low accumulation of DNA lesions. The low apoptosis threshold was mediated by constitutive p53 expression and a marked upregulation of proapoptotic p53 target genes of the BCL-2 family, ensuring the efficient iPSC removal upon genotoxic insults. Intriguingly, despite the elevated apoptosis sensitivity, both mitochondrial and nuclear DNA lesions induced by genotoxins were less frequent in iPSCs compared to fibroblasts. Gene profiling identified that mRNA expression of several antioxidant proteins was considerably upregulated in iPSCs. Knockdown of glutathione peroxidase-2 and depletion of glutathione impaired protection against DNA lesions. Thus, iPSCs ensure genomic integrity through enhanced apoptosis induction and increased antioxidant defense, contributing to protection against DNA damage.


Enantioselective effects of alpha-hexachlorocyclohexane (HCH) isomers on androgen receptor activity in vitro.
Alpha-hexachlorocyclohexane (alpha-HCH), a part of the HCH pesticide mixture, is one of the most widespread persistent organic pollutants. Interestingly, only limited number of studies addressed the toxicity of alpha-HCH and the effects of its individual optical isomers have not been investigated in detail. In the present study we separated two alpha-HCH enantiomers by preparative HPLC and studied their activities towards androgen receptor (AR) using the MDA-kb2 cell line stably transfected with the luciferase reporter gene under the control of AR. There was no direct effect of alpha-HCH on AR but both isomers significantly suppressed the activity of AR in co-exposure with the natural ligand dihydrotestosterone in a concentration-dependent manner. One of the enantiomers appeared to be more active at lower concentration, which was also supported by the molecular modeling calculations with AR that showed a slight difference in estimated free energy of binding and inhibition constant between two enantiomers. Although studies with other pesticides demonstrated strong enantioselective differences in toxicity, the present research shows rather minor differences in modulations of AR by both alpha-HCH enantiomers. For the first time, enantioselective effects of alpha-HCH were demonstrated and the results suggest interaction with multiple regulatory events controlling the AR activity. Full elucidation of the toxicity mechanism will require further research.


Antiphospholipid antibodies in relation to sterility/infertility.
Of the systemic autoimmune diseases that lead to sterility/infertility, antiphospholipid syndrome (APS) has an outstanding importance; it may be associated with abortion and premature birth which are included in its diagnostic criteria, as well as preeclampsia, pregnancy-induced hypertension, foetal retardation, miscarriage, stillbirth and sterility. Between 2004 and 2009, on the Department of Immunology in the Zala County Hospital, 100 female patients with sterility (st)/infertility (if) (33/67), (mean age: 34.08 years) underwent, in addition to history taking and physical examination, an assessment by immune-serologic tests (ANA, anti-dsDNA, ENA-Profile, anti-TPO, a-sperm, aCL, aPS, aβ2GP1, aANX, and aPT). Positive aCL on two occasions could be demonstrated in 27/100 cases (27%) (st/if: 7/20). Among them 4 cases of primary APS have been diagnosed respectively. In the remaining 17 patients the clinical picture did not fulfil criteria. In addition to the twofold positive aCL, unusual antiphospholipid antibodies including aβ2GP1, aPS or both were present in 1/27, 2/27 and 1/27 patients, as well as aANX and aPT in 3/26 and 1/27 patients respectively. One-time positive aCL occurred in 16/100 women (16%) (st/if: 5/11); among them aPT and aβ2GP1 could be detected in 1/16 patient each. Based on the clinical picture, we raised the possibility of primary APS in 2/16 patients. Among the aCL-negative women, we found the unusual antibodies of APS in 8/57 patients (14%) including positivity of aβ2GP1, aPS, aPT and aANX in 4/57, 4/57, 2/57 and 3/57 patients respectively; taking the clinical criteria of APS into consideration, primary APS could be stated in 2/57 patients of them. The 32 pregnancies developed in the follow-up period upon administration of acetylsalicylic acid (ASA) and maintenance dose low molecular weight heparin (LMWH), together with prednisolone in patients with secondary APS, resulted in 23 deliveries and 5 miscarriages; 4 pregnancies are currently in progress. The results of our investigations highlight the significance of demonstrating latent autoimmune diseases in female patients with sterility/infertility, as barrenness can be terminated by the appropriate treatment of these conditions.


Discovery of the genus Vanhartenidia Lelej, 2006 (Hymenoptera: Mutillidae) in Egypt, with description of a new species.
The genus Vanhartenidia Lelej, 2006 is newly recorded from Egypt. A new species, V. mandishaensis El-Torkey & Soliman, sp. nov. is described and illustrated from Bahariya Oasis (Giza, Egypt).


Prognostic Value of Nonalcoholic Fatty Liver Disease in Patients With Severe Aortic Stenosis Who Underwent Transcatheter Aortic Valve Implantation.
Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular events. Although the association between NAFLD and aortic valve sclerosis has been described, the prevalence and prognostic implications of NAFLD among patients with severe aortic stenosis (AS) have not been described. In addition, the effect of the presence of severe tricuspid regurgitation (TR) on the prevalence of NAFLD remains unexplored. Accordingly, we investigated the prognostic implications of NAFLD among patients with severe AS with and without concomitant significant TR. A total of 538 patients (aged 80 ± 7 y, 49.6% men) who underwent noncontrast computed tomography before transcatheter aortic valve implantation (TAVI) between 2007 and 2019 were included. NAFLD was defined as a liver-to-spleen attenuation ratio <1.0 on noncontrast computed tomography. NAFLD was present in 118 patients (21.9%). There were no significant differences in pulmonary arterial pressure, right atrial pressure, or the prevalence of significant TR between patients with and without NAFLD. During a median follow-up of 47 months (interquartile range 20 to 70 months), 224 patients (41.6%) died. Univariate Cox regression analysis demonstrated that NAFLD was not significantly associated with all-cause death among patients treated with TAVI (hazard ratio 1.32, 95% confidential interval 0.97 to 1.79, p = 0.07). In conclusion, among patients with severe AS who underwent TAVI, the prevalence of significant TR and the clinical outcomes were similar in patients with and without NAFLD.


Developmental changes in the expression of growth-associated protein-43 mRNA in the monkey thalamus: northern blot and in situ hybridization studies.
The expression of growth-associated protein-43 has been related to axonal elongation and synaptic sprouting. Using the Northern blot analysis, we investigated the developmental changes of growth-associated protein-43 mRNA in the thalamus of macaque monkeys. The amount of growth-associated protein-43 mRNA was high at embryonic day 125, and decreased at postnatal day 1. It increased again at postnatal day 8, reached its peak value at postnatal days 50-70, and then decreased gradually until postnatal year 1. We previously reported that the amount of growth-associated protein-43 mRNA in the cerebral cortex decreased roughly exponentially during perinatal and postnatal periods and that it approached the asymptote by postnatal day 70 [Oishi T, Higo N, Umino Y, Matsuda K, Hayashi M (1998) Development of GAP-43 mRNA in the macaque cerebral cortex. Dev Brain Res 109:87-97]. The present findings may indicate that extensive synaptic growth of thalamic neurons continues even after that of cortical neurons has finished. We then performed in situ hybridization to investigate whether the expression level of growth-associated protein-43 mRNA was different among various thalamic nuclei. In the infant thalamus (postnatal days 70-90), moderate to intense expression of growth-associated protein-43 mRNA was detected in all thalamic nuclei. Quantitative analysis in the infant thalamus indicated that the expression levels were different between the nuclear groups that are defined by the origin of their afferents. The expression in the first order nuclei, which receive their primary afferent fibers from ascending pathways [Guillery RW (1995) Anatomical evidence concerning the role of the thalamus in corticocortical communication: a brief review. J Anat 187 (Pt 3):583-592], was significantly higher than that in the higher order nuclei. While moderate expression was also detected in the adult dorsal thalamus, the expression in the first order nuclei was almost the same as that in the higher order nuclei. Thus, the in situ hybridization experiments indicated that the transient postnatal increase in the amount of growth-associated protein-43 mRNA, which was shown by the Northern blot analysis, was mainly attributed to enhanced expression in the first order nuclei during the postnatal period. This may be a molecular basis for environmentally induced modification of thalamocortical synapses.


Suspended scattering particles in motion using OCT angiography in branch retinal vein occlusion disease cases with cystoid macular edema.
We aimed to investigate the clinical implication of suspended scattering particles in motion (SSPiM) using optical coherence tomography angiography (OCTA) among branch retinal vein occlusion disease (BRVO) cases with macular edema (ME). Medical records of BRVO patients were reviewed. Central retinal thickness (CRT), ME type, and cyst size on optical coherence tomography images were evaluated before and after intravitreal bevacizumab injection. Nonperfusion area, SSPiM, and microvascular abnormalities in OCTA images were evaluated using a Heidelberg machine. SSPiM was identified in 24 of 56 cases. There were no differences in baseline characteristics between groups with and without SSPiM. Disease duration, disease-free duration, previous injection number, microaneurysms in the superficial vascular complex, and microaneurysms in the deep vascular complex (DVC) (p = 0.003, 0.013, 0.028, 0.003, < 0.001, respectively) differed significantly between the two groups. After multivariate logistic analysis, microaneurysms in the DVC were the only different factor between the two groups (odds ratio [OR]: 0.091; p = 0.001). Furthermore, SSPiM in the DVC (OR 10.908; p = 0.002) and nonperfusion grade (OR 0.039; p < 0.001) were significantly associated with cyst response after intravitreal injection. SSPiM may be correlated with microaneurysms in the DVC and a poor anatomical response after intravitreal injection.


Antibiotic resistance genes detected in the marine sponge Petromica citrina from Brazilian coast.
Although antibiotic-resistant pathogens pose a significant threat to human health, the environmental reservoirs of the resistance determinants are still poorly understood. This study reports the detection of resistance genes (ermB, mecA, mupA, qnrA, qnrB and tetL) to antibiotics among certain culturable and unculturable bacteria associated with the marine sponge Petromica citrina. The antimicrobial activities elicited by P. citrina and its associated bacteria are also described. The results indicate that the marine environment could play an important role in the development of antibiotic resistance and the dissemination of resistance genes among bacteria.


Nonoperative initial management versus silon chimney for treatment of giant omphalocele.
Giant omphalocele is a major clinical challenge for pediatric surgeons. Whereas small- to medium-sized defects can be repaired primarily, larger omphaloceles cannot be closed at birth because the liver and small bowel have lost the right of domain to the abdomen. Two divergent strategies have evolved for treating these giant defects: (1) use of a silon chimney with gradual reduction of the contents of the sac, and (2) initial nonoperative management (epithelialization) of the omphalocele followed by repair of the residual ventral hernia. In an 18-year retrospective study, we have reviewed our experience with these treatment methods. Ninety-four infants underwent treatment for omphalocele between 1975 and 1993. Primary closure (PC) was possible in 55 patients, silon chimney (SC) was used in 15, and 7 had nonoperative management (NM) with epithelialization. In the remaining 17 infants, surgery was believed to be inappropriate because of the lethality of their associated anomalies. Major (but potentially survivable) anomalies were present in 26% of PC, 13% of SC, and 71% of the NM group patients. The majority of the liver was present in 73% of SC- and 86% of NM-treated omphaloceles. There was a decrease in length of stay, time to enteral feeding, and mortality over the 18-year period. However, those patients whose defects could not be closed primarily had consistently longer hospital stays. This was particularly true for the SC patients. The decreased use of total parenteral nutrition seems to reflect a shift from SC to NM rather than a decrease in the interval to full enteral feeding in any given treatment group over time.(ABSTRACT TRUNCATED AT 250 WORDS)


Trends in the prevalence and treatment of bipolar affective disorder in South Korea.
This study aimed to assess trends in the prevalence of bipolar disorder (BP). We also analyzed patterns of medical use by Korean patients with BP, defined as those diagnosed with the International Classification of Diseases (ICD) F31 code who used at least one inpatient or outpatient medical service in a year. We analyzed yearly BP prevalence and inpatient hospitalization periods per year from 2008 to 2017 using National Health Insurance Service (NHIS) claims data for 52.43 million people. Overall, the BP prevalence was 0.2 %, as of 2017, with consistently higher rates in women. The BP prevalence was highest among those aged ≥60 years (0.27 %) and was lowest among those aged 0-29 years (0.12 %), as of 2017. The average annual rate of increase among those aged 0-29 years and ≥60 years was 8.48 % and 7.39 %, respectively, which exceeded the overall mean of 6.58 %. The average annual rate of increase in BP prevalence for those aged 30-59 years was 4.67 %. The proportion of inpatients who were hospitalized for longer than 180 days decreased, while the proportion of those hospitalized for 0-14 days increased. The estimated BP prevalence was higher when using the most recent NHIS data rather than in the surveys. These prevalence rates can be used to support the development of future mental health policies.


Antibody response to immunization with purified GD3 ganglioside and GD3 derivatives (lactones, amide and gangliosidol) in the mouse.
GD3 is the ganglioside most abundantly expressed on the cell surface of human melanoma, and treatment with a monoclonal antibody recognizing GD3 has induced major responses in a small proportion of patients. However, we have been unable to induce production of GD3 antibodies in melanoma patients by active immunization with GD3-expressing melanoma cells or purified GD3. In this report we describe attempts to increase the immunogenicity of GD3 in the mouse by chemical modification. GD3 lactone I and II, GD3 amide and GD3 gangliosidol were synthesized, and the humoral immune response to these derivatives was compared with the response to unmodified GD3. The GD3 derivatives were more immunogenic than GD3. At a low dose all congeners induced an IgM response, with antibody titers higher than those elicited by low-dose GD3. The gangliosidol and amide derivatives also induced an IgG response. IgM antibodies induced by immunization with GD3 lactone I cross-reacted with purified GD3 and GD3-expressing melanoma cells. Titers of GD3 cross-reactive antibodies were slightly higher than after immunization with GD3 itself at the same low dose. IgM and IgG antibodies induced by the other congeners did not cross-react with GD3.


Thalamic Tumors in a Pediatric Population: Surgical Outcomes and Utilization of High-Definition Fiber Tractography and the Fiber Tracking Technique.
This study aimed to assess the operability of thalamic tumors since they are generally considered to be inoperable and to have poor outcomes. Advancements in neuroimaging, neuronavigational technology, and intraoperative neurophysiological monitoring allow accurate planning and safe resection. Clinical data and reports of 10 pediatric patients with thalamic tumors were retrieved retrospectively. All 10 patients underwent surgical intervention. Diffusion tensor tractography (DTI) was used preoperatively to select the safest surgical route. Intraoperative MRI and postoperative MRI were used to evaluate the extent of resection. There were three gross total resections (GTRs), two subtotal resections (STRs), two partial resections (PRs), and three biopsies. All patients had unilateral thalamic tumors. Different surgical approaches were used according to the relationship with the internal capsule and corticospinal tract and according to the preoperative DTI. Five patients had pilocytic astrocytoma, two had diffuse pediatric-type high-grade glioma, one had ganglioglioma, one had pediatric-type diffuse low-grade glioma, and one had atypical teratoid rhabdoid tumor (ATRT). The outcomes of low-grade tumors were favorable, especially for those who underwent resection, and those of high-grade tumors were poor regardless of the extent of resection. Our review shows that surgical resection of thalamic tumors can be done safely and offers favorable outcomes for patients with low-grade tumors, even without adjuvant therapy. Our study provides further evidence for thalamic tumors operability and safe resection.


Loss of RPS41 but not its paralog RPS42 results in altered growth, filamentation and transcriptome changes in Candida albicans.
Although ribosomal proteins (RPs) are components of the ribosome, and function centrally in protein synthesis, several lines of evidence suggest that S4 ribosomal proteins (Rps4ps) can function in other cellular roles. In Candida albicans, ribosomal protein S4 (Rps4p) is encoded by two distinct but highly similar genes, RPS41 (C2_10620W_A) and RPS42 (C1_01640W_A). Previous studies indicated that in Saccharomyces cerevisiae loss of one isoform generated distinct phenotypes. To probe this relationship in C. albicans, rps41Δ and rps42Δ homozygous null mutants were generated. The transcript levels of the RPS41 and RPS42 genes are asymmetric in C. albicans, RPS41 mRNA levels were similar in wild-type strains and rps42Δ null mutants, while RPS42 gene transcript levels were induced 20 fold relative to wild type in rps41Δ null mutants. We found that the rps41Δ homozygous null mutant showed a reduced growth rate, and had defects in filament formation in liquid media and on solid media, while these phenotypes were not observed in the rps42Δ mutant strain. Neither the rps41Δ nor rps42Δ mutant strains displayed differential sensitivity to azoles, although intriguingly ectopic expression of either RPS41 or RPS42 in a wild-type strain leads to decreased sensitivity to fluconazole (FLC). C. albicans cDNA microarray analysis experiments found that carbohydrate and nitrogen metabolic processes were repressed but transport-process-related genes were up-regulated in the rps41Δ mutant. Overall, our present study suggests that loss of the RPS41 gene but not its paralog the RPS42 gene can generate distinct phenotypes including effects on growth rate, morphological transitions, and susceptibility to osmotic stress due to the fact that mRNA levels of RPS41 is much higher than RPS42 in C. albicans.


Efficacy of experimental trypanocidal compounds against a multiple drug-resistant Trypanosoma brucei brucei stock in mice.
Several experimental trypanocidal compounds, 6-amidino-2-(4-amidinophenyl)indole dilactate (DAPI), DL-alpha-difluoromethylornithine (DFMO), 2-(dimethylamino)-4'-[(1-methyl-2-nitroimidazole-5-yl) methoxy] aceto-anilide (Ro 15-0216), sinefungin, and triacetylbenzene-tris(guanylhydrazone)trimethanesulfonate hydrate (TBG-MS) were tested to evaluate their ability to cure mouse infections with a multiple drug-resistant Trypanosoma brucei brucei stock (CP 547). This stock proved to be drug-resistant against diminazene aceturate, homidium chloride, isometamidium, quinapyramine sulfate, Mel B, and pentamidine isethionate but fully sensitive to suramin. Compared with the sensitive stock CP 462, the drug-resistant stock CP 547 was completely resistant to 16-fold the curative dose of sinefungin and partially resistant to 4-fold the curative dose of DAPI and to 13-fold the curative dose of TBG-MS, a dose that killed 25% of the animals due to its toxicity. Ro 15-0216 cured all mice when 18 times the usual curative dose level was given. DFMO was equally effective against both stocks.


Plasma chemistry reference values in ostriches.
Reference values for 18 plasma chemical variables in blue neck ostriches (Struthio camelus australis, n = 60, age 24-36 mo) were established for use in veterinary clinical practice using nonparametric statistics. The following values were established for the percentiles P2.5 and P97.5: sodium 147-157 mmol/L, calcium 2.4-4.8 mmol/L, inorganic phosphate 1.3-2.3 mmol/L, chloride 94-105 mmol/L, glucose 10.3-13.7 mmol/L, urea 0.5-0.8 mmol/L, uric acid 351-649 mumol/L, bile acids 8-33 mumol/L, total protein 39-56 g/L, albumin-globulin ratio 0.45-0.59, osmolality 304-330 mOsm/kg, alkaline phosphate 69-217 IU/L, aspartate aminotransferase 243-418 IU/L, gamma-glutamyltransferase 0-1 IU/L, creatine kinase 1648-4894 IU/L, glutamate dehydrogenase 8-17 IU/L, and lactate dehydrogenase 860-2236 IU/L. The plasma calcium concentration was significantly (P < 0.001; r = 0.74) related to the total protein concentration and an adjustment-formula for calcium was derived: adjusted Ca (mmol/L) = Ca (mmol/L)--0.09 TP (g/L) + 4.4. The influence of blood sample treatment on the plasma potassium concentration as seen in other avian species was demonstrated in a separate experiment, emphasizing the need to separate plasma and cells immediately after collection in avian blood samples.


Cardio protective role of wogonin loaded nanoparticle against isoproterenol induced myocardial infarction by moderating oxidative stress and inflammation.
Wogonin, one of the main active ingredients of Scutellaria radix, is a kind of flavonoid compound. In the present study, we report that wogonin nanoparticles (Wog np) protect Isoproterenol (ISO) induced Myocardial Infarction (MI) rats. Nanoparticles of sizes less than 200 nm with spherical shape were prepared using Polylactic-co-glycolic acid (PLGA) and Polyvinyl alcohol (PVA) respectively as polymer and stabilizer. Male Wistar rats were divided into 4 groups. Group 1 as a control group administered with physiological saline solution with 0.5 % carboxymethylcellulose (1 mL/day). Group 2 served as toxic group; rats received physiological saline solution with 0.5 % carboxymethylcellulose (1 mL/day) orally for 21 days Groups 3 and 4 received Wog np (25 and 50 mg/kg/day) orally for 21 days and on the 20th and 21 st days group 2, 3, and 4 were administered with ISO (85 mg/kg) through s.c. route at 24 h interval. pre-treatment with Wog np (25 and 50 mg/kg) could significantly reduce the cardiac infarct size, serum cardiac markers, lipid peroxidation product (MDA) and inflammatory markers as well as markedly upregulated the protein expression of nuclear factor erythroid 2-related factor (Nrf2)and heme oxygenase-1 (HO-1) to confer its strong cardioprotective activity against ISO induced myocardial damage.


Propolis protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity in rat hepatocytes.
The present experiment was undertaken to determine the effectiveness of propolis in alleviating the toxicity of TCDD on cultured primary rat hepatocytes. Propolis (25, 50 and 100 μM) was added to plain culture or simultaneously with TCDD (5 and 10 μM). The hepatocytes were treated with TCDD and propolis for 48 h. Then cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by liver micronucleus assay (LMN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD decreased cell viability. TCDD also increased TOS level and decreased TAC level in rat hepatocytes. On the basis of increasing doses, the TCDD caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG levels as compared to control culture. In cultures treated with propolis alone, cell viability and TOS level were not affected, while the level of TAC was significantly increased in dose-dependent fashion. The presence of propolis with TCDD modulated its toxic effects on primary hepatocytes cultures. Noteworthy, propolis has a protective effect against TCDD-mediated DNA damages.


The optimal timing of radiotherapy in the combination treatment of limited-stage extranodal natural killer/T-cell lymphoma, nasal type: an updated meta-analysis.
This study was designed to explore the relative efficacy and toxicity of upfront radiotherapy (RT) and late RT in combination treatments for patients with limited-stage extranodal natural killer/T-cell lymphoma nasal type (LS-ENKTL). We searched for clinical trials in the PubMed database that compared upfront RT with late RT in the combined treatment of patients with LS-ENKTL. We systematically evaluated the differences in survival, treatment response, and treatment-related adverse events (AEs) between these two groups. Ten retrospective studies with a total of 1752 patients were included. Upfront RT significantly prolonged the overall survival (OS) and progression-free survival (PFS) of patients compared to late RT in combination with chemotherapy (CT) (HR = 0.72, 95% CI 0.59-0.88, P = 0.001 for OS; HR = 0.57, 95% CI 0.41-0.79, P = 0.0007 for PFS). The complete remission (CR) rate in the upfront RT group was superior to that in the late RT group (HR = 1.61, 95% CI 1.09-2.37, P = 0.02). Patients experienced similar local recurrence-free survival (LRFS), objective response rates (ORR), and toxicity between these two arms (P > 0.05 for all) in the analysis of each subgroup. The survival benefit of upfront RT was not correlated with the RT dose, concurrent chemoradiotherapy (CCRT) (or not), or the CT regimen (P > 0.05 for all). Without compromises in terms of toxicity, RT dose, and treatment modality, upfront RT can significantly benefit OS, PFS, and CR compared to late RT in combination treatment. These findings verified that the upfront RT regimen is more suitable for patients with LS-ENKTL.


Modelling HIV/AIDS and monkeypox co-infection.
During the last two decades, reports on emerging human monkeypox outbreaks in Africa and North America have reminded us that beside the eradicated smallpox there are other pox viruses that have great potential to harm people. A deterministic model for the co-infection of HIV/AIDS and monkeypox is formulated and analysed. The endemic equilibria are shown to be locally and globally asymptotically stable using the Centre Manifold theory and the Lyapunov function approach, respectively. Analysis of the basic reproduction numbers and numerical simulations suggest that an increase in the number of monkeypox in the animal species results in an increase of the number of people having monkeypox. Threshold conditions that determine the competitive outcomes of the two diseases are provided. Furthermore, numerical simulations using a set of reasonable parameter values support the claim that HIV infection greatly enhances monkeypox infection and vice versa.


PFAS and DOM removal using an organic scavenger and PFAS-specific resin: Trade-off between regeneration and faster kinetics.
Treatment technologies such as ion exchange (IX) process exhibit promising potentials for the removal of toxic per- and poly-fluoroalkyl substances (PFAS) from natural waters. In recent years, industries have started manufacturing PFAS-specific resins which are typically operated in a single use-and-dispose mode until exhaustion. However, this increases the resin demand and the consequent operational cost and environmental burden of the IX process. In this study, the performance of a PFAS-specific resin (A592) was compared with that of a regenerative organic scavenger resin (A860) which is traditionally employed for dissolved organic matter (DOM) and micorpollutant removal. Comparative studies were performed to examine the removal of multiple long- and short-chain carboxylic, sulfonic, precursor and emerging PFAS (including GenX) from synthetic and natural waters. The A592 resin exhibited faster uptake kinetics for PFAS while simultaneously removing 10-15% of DOM. The A860 resin removed ~60-70% of DOM; however, it required approximately 3-fold higher contact times for achieving the same degree of PFAS removal when compared to the PFAS-specific resin. The resin breakthrough (Ctreated (PFAS) > 70 ng/L) was observed around 125,000 ± 5000 bed volumes (BVs) for the PFAS-specific resin (via multiple loading tests), while it ranged between 15,000-27,000 BVs for the organic scavenger. Yet, a mass balance on PFAS and DOM removal indicated ~90-98% site saturation (in milli-equivalents (meqs)) on both IX resins before exhaustion. More importantly, the regenerated organic scavenger resin (A860) exhibited PFAS and DOM removal capabilities for longer operational BVs when compared to A592 operated in a single-use-mode in natural waters.


Quantitative and Qualitative Evaluation of The Structural Designing of Medical Informatics Dynamic Encyclopedia.
Encyclopedias and their compilation have become so prevalent as a valid cultural medium in the world. The daily development of computer industry and the expansion of various sciences have made indispensable the compilation of electronic, specialized encyclopedias, especially the web-based ones. This is an applied-developmental study conducted in 2014. First, the main terms in the field of medical informatics were gathered using MeSH Online 2014 and the supplementary terms of each were determined, and then the tree diagram of the terms was drawn based on their relationship in MeSH. Based on the studies done by the researchers, the tree diagram of the encyclopedia was drawn with respect to the existing areas in this field, and the terms gathered were put in related domains. In MeSH, 75 preferred terms together with 249 supplementary ones were indexed. One of the informatics' sub-branches is biomedical informatics and health which itself consists of three sub-divisions of bioinformatics, clinical informatics, and health informatics. Medical informatics which is a subdivision of clinical informatics has developed from the three fields of medical sciences, management and social sciences, and computational sciences and mathematics. Medical Informatics is created of confluence and fusion and applications of the three major scientific branches include health and biological sciences, social sciences and management sciences, computing and mathematical sciences, and according to that the structure of MeSH is weak for future development of Encyclopedia of Medical Informatics.


Direct sound printing.
Photo- and thermo-activated reactions are dominant in Additive Manufacturing (AM) processes for polymerization or melting/deposition of polymers. However, ultrasound activated sonochemical reactions present a unique way to generate hotspots in cavitation bubbles with extraordinary high temperature and pressure along with high heating and cooling rates which are out of reach for the current AM technologies. Here, we demonstrate 3D printing of structures using acoustic cavitation produced directly by focused ultrasound which creates sonochemical reactions in highly localized cavitation regions. Complex geometries with zero to varying porosities and 280 μm feature size are printed by our method, Direct Sound Printing (DSP), in a heat curing thermoset, Poly(dimethylsiloxane) that cannot be printed directly so far by any method. Sonochemiluminescnce, high speed imaging and process characterization experiments of DSP and potential applications such as remote distance printing are presented. Our method establishes an alternative route in AM using ultrasound as the energy source.


Sorption and degradation of contaminants of emerging concern in soils under aerobic and anaerobic conditions.
Large quantities of contaminants of emerging concern (CECs) are susceptible of entering the terrestrial environments through the application of recycled wastewater, manures, and biosolids, resulting in their progressive contamination and possible long-term effects over terrestrial species. Many studies on the environmental fate of CECs focus on aquatic environments and/or wastewater treatment plants, but little is still known about their behavior at environmentally relevant concentrations in agricultural soils. In this study, we evaluated the adsorption and degradation of nine different pharmaceuticals (nadolol, sulfamethizole, sulfamethoxazole, sulfamethopyridazone, carbamazepine, ibuprofen, diclofenac, hydrochlorothiazide, and gemfibrozil) and four artificial sweeteners (acesulfame, saccharin, cyclamate, and sucralose) in two soils under aerobic and anaerobic conditions. The sorption of target compounds in soils fitted well to a Freundlich isotherm model and was relatively low (Kf < 200 L kg-1). Sorption was highest for cyclamate (Kf = 162 L kg-1) and acesulfame (Kf = 156 L kg-1), while lowest sorption coefficients were measured for ibuprofen (Kf = 1-7 L kg-1). All target compounds (except for carbamazepine) were susceptible to microbial degradation under aerobic conditions, with half-lives ranging from 1 to 18 days. Degradation occurred at a higher rate under aerobic conditions for most contaminants, but they were relatively persistent under anaerobic conditions. For instance, over 90% of the initial amount of spiked nadolol was degraded in aerobic soils after 4 days of incubation, while only 18-24% was lost in absence of oxygen after 1 month, resulting in t1/2 values between 95 and 103 days. The degradation behavior of the target compounds varied in relation to soil and compound physicochemical properties as well as the microbial activities (e.g., 220 ppm of CH4 were produced in anaerobic experiments) and aeration of the tested soils. Overall, the poor adsorption and relative persistence of sucralose and carbamazepine suggests that both may be used as potential tracers for soil and groundwater contamination.


[Clinical-experimental substantiation of preparation Kollost and bioresorbable membranes Diplen-Gum and Parodoncol use in cases of retained and dystopic mandibular third molar].
Research is devoted to study of the efficiency of osteoplastic means use at surgical interventions in oral cavity in comparison with healing of a bone wound under a blood clot. The data of experimental research and examples of clinical use of osteoplastic materials and bioresorbable membranes are presented.


Interaction of humic acids with human DNA: proposed mechanisms and kinetics.
Human DNA quantification by quantitative real-time PCR (QRT-PCR) has gained great importance in forensic DNA and ancient DNA studies. However, in such samples, DNA quantification is impaired by the frequently present humic acid (HA). We have previously shown that the addition of synthetic HA inhibits QRT-PCR. In this study we investigated the possible mechanisms of HA interaction with human DNA, and kinetics of QRT-PCR inhibition. In QRT-PCR with pure human DNA and no HA added, VMAX was 40. With DNA sample containing 4 microg/mL of HA, VMAX was 30.30 while the addition of extra Taq polymerase to the same sample changed VMAX into 38.91, amplifying between 80 and 90% of input DNA. The KM/VMAX ratio in all the samples remained constant, indicating that the mechanism of HA inhibition of QRT-PCR is uncompetitive by nature. Moreover, HA shifts the human DNA melting temperature point (Tm) from 75 to 87 degrees C and inhibits DNase I-mediated DNA cleavage, most probably affecting the enzyme's activity.


Diabetic heart and kidney exhibit increased resistance to lipid peroxidation.
Alloxan-diabetic rats and age-matched controls were killed after 6 weeks of diabetes; heart and kidneys were removed and assayed for thiobarbituric acid-reactive substances (TBARS), lipid hydroperoxides, lipid phosphorus, total fatty acid composition and glutathione. Tissue homogenates from a second group of diabetic and control rats were incubated in oxygen-saturated buffer with and without the free radical generating system Fe2+/ascorbate (0.1/1.0 mM) and were assayed for lipid peroxidation. Diabetic hearts contained markedly lower levels of TBARS and lipid hydroperoxides (40% and 18%, respectively) than control hearts, whereas differences in TBARS were less pronounced in kidneys (9%). Incubation of homogenates of both organs in the presence or absence of Fe2+/ascorbate for up to 2 h yielded significantly lower levels of TBARS and lipid hydroperoxides with diabetic tissue. Diabetic hearts and kidneys contained higher levels of glutathione (28% and 13% over controls) and both diabetic tissues showed much higher linoleate/arachidonate ratios than did the controls (9.86 vs. 2.56 for heart, 2.01 vs. 0.86 for kidney). We conclude that diabetic tissues develop enhanced defense systems against oxidative stress and we assume tha the lower levels of arachidonate contribute to their resistance to lipid peroxidation as well.


Establishing validity of the fundamentals of spinal surgery (FOSS) simulator as a teaching tool for orthopedic and neurosurgical trainees.
Pedicle screw placement is a demanding surgical skill as a spine surgeon can face challenges including variations in pedicle morphology and spinal deformities. Available CT simulators for spine pedicle placement can be very costly and hands-on cadaver courses are limited by specimen availability and are not readily accessible. To conduct validation of a simulated training device for essential spine surgery skills. Cross-sectional, empirical study of physician performance on a surgical simulator model. Spine attending physicians and residents from four different academic institutions across the United States. Performance metrics on two surgical simulator tasks. After IRB approval, an inexpensive ($30) simulator was developed to test two main psychomotor tasks (1) creation of the pedicle screw path with a standard gearshift probe without cortical breaks and (2) the ability to palpate for the presence or absence of cortical breaches as well as determine the location of wall defects. Orthopedic and neurosurgery residents (N=72) as well as spine attending surgeons (N=26) participated from four different institutions. To test construct validity, performance metrics were compared between participants of different training status through one-way analysis of variance and linear regression analysis, with significance set at p<.05. Spine attending surgeons consistently scored higher than the residents, in the screw trajectory task with triangular base (p=.0027) and defect probing task (p=.0035). In defect probing, performance improved with linear trend by number of residency training years with approaching significance (p=.0721). In that task, independent of institutional affiliation, PGY-2 residents correctly identified an average of 1.25±0.43 fewer locations compared with attending physicians (p=.0049). More than 80% of the spine attendings reported they would use the simulator for training purposes. This low-cost fundamentals of spine surgery simulator detected differences in performances between spine attending surgeons and surgical residents. Programs should consider implementing a simulator such as fundamentals of spine surgery to assess and develop pedicle screw placement ability outside of the operating room.


Detection of two classes of Ca2+ binding sites in troponin C with circular dichroism and tyrosine fluorescence.
We have observed a biphasic increase in [theta]222 and the tyrosine fluorescence of troponin C (TnC) with increasing [Ca2+]. Approximately 62% of the total helical change and 81% of the total increase in tyrosine fluorescence occurred with Ca2+ binding to a class of sites with a KCa of approximately 2.7 X 10(7) M-1. The remaining spectral changes occurred with Ca2+ binding to a class of sites with KCa of approximately 3.1 X 10(5) M-1. We interpret these biphasic responses in terms of distinct structural changes occurring in TnC with Ca2+ binding to the high affinity (KCa approximately 2.1 X 10(7) M-1) Ca2+-Mg2+ sites and to the low affinity (KCa approximately 3.2 X 10(5) M-1) Ca2+-specific regulatory sites.


Intracapsular hip fractures in patients with rheumatoid arthritis.
We reviewed the treatment of 43 patients with rheumatoid arthritis and femoral neck fracture. Patients' average age was 66.4 (36-80) years and average duration of RA was 20.3 (4-42) years. Thirteen patients were treated with primary total hip arthroplasty (THA), and the clinical results were comparable to patients treated conservatively or by osteosynthesis. Eighteen patients were treated with primary bipolar hip prosthesis and after an average of 6.1 (1-13) years there was no acetabular destruction. However, long-term results were inferior to patients treated with THA. Nine patients were treated with osteosynthesis, of which two later had a hip prosthesis. Three cases with impacted fractures were treated conservatively with successful union in all.


Development of an effective method of human DNA extraction from soil as forensic evidence.
In forensic investigations, it is crucial to detect a suspect's DNA from the available evidence. In an outdoor crime scene, the evidence may be mixed with the soil. However, soil is speculated to inhibit DNA extraction from forensic science samples. In the field of soil microbiology, it is necessary to extract DNA directly from soil to analyse its microbial composition. In this study, we investigated whether skim milk used in procedure of DNA extraction from soil samples could be applied to forensic science to enhance human DNA extraction efficiency from soil mixed with forensic evidence, such as blood, buccal cells, and skin cells. The use of additive reagents, skim milk and bovine serum albumin (BSA), are known to blocking reagent. In the selection of additive reagents experiment, about blood sample, using the skim milk and BSA were found to increase the DNA yield. Therefore, we observed extracted DNA yield from blood, buccal cells, and skin cells when skim milk and BSA were used as additive reagents. The DNA recovery rate was high across all samples upon addition of skim milk. However, in STR analysis, a non-specific peak was detected in the extracted DNA in the presence of skim milk, which was not detected in the presence of BSA, indicating its suitability in forensic analysis. Our study suggests that addition of BSA can efficiently aid the extraction of DNA from forensic evidence mixed with soil.


Evaluation of the Cal antibody in the detection of malignant cells in fine needle aspirates from breast lumps.
In a study involving 86 fine needle cell aspirates from patients with breast lumps attending a primary Breast Referral Clinic, we have been unable to confirm that cellular binding of Cal antibody reliably differentiates between benign and malignant disease of the breast. The test carried unacceptable predictive values (46% when positive and 70% when negative). The false positive and negative rates were 47.2% and 36.4% respectively. A skilled cytologist using conventional Papanicolaou staining gave a much more accurate interpretation of the benign or malignant nature of the aspirates than did Cal antibody binding.


Coronary degeneration in sexually mature rainbow and steelhead trout, Salmo gairdneri.
Correlation of coronary arteriosclerosis with sexual maturation was found in rainbow and steelhead trout. All sexually mature nonanadromous rainbow, precocial male steelhead, and adult spawning steelhead had myointimal hyperplasia but it was infrequent in immature juveniles. Lesion severity in adult rainbow and precocial steelhead approach that of spawning steelhead.


Effects of alprazolam on the development of MTV-induced mammary tumors in female mice under stress.
Female C3H/He mice carrying the mammary tumor virus (MTV) were monitored for mammary tumor incidence and latent periods while subjected to a daily intraperitoneal (i.p.) injection of placebo or alprazolam (1 mg/kg per day). Although all of the mice were potential candidates for MTV-induced breast cancer, those injected with alprazolam were partially protected against adverse effects of stress induced by the daily administration of placebo.