Genetic basis of growth reaction to drought stress differs in contrasting high-latitude treeline ecotones of a widespread conifer.
Climate change is increasing the frequency and intensity of drought events in many boreal forests. Trees are sessile organisms with a long generation time, which makes them vulnerable to fast climate change and hinders fast adaptations. Therefore, it is important to know how forests cope with drought stress and to explore the genetic basis of these reactions. We investigated three natural populations of white spruce (Picea glauca) in Alaska, located at one drought-limited and two cold-limited treelines with a paired plot design of one forest and one treeline plot. We obtained individual increment cores from 458 trees and climate data to assess dendrophenotypes, in particular the growth reaction to drought stress. To explore the genetic basis of these dendrophenotypes, we genotyped the individual trees at 3000 single nucleotide polymorphisms in candidate genes and performed genotype-phenotype association analysis using linear mixed models and Bayesian sparse linear mixed models. Growth reaction to drought stress differed in contrasting treeline populations. Therefore, the populations are likely to be unevenly affected by climate change. We identified 40 genes associated with dendrophenotypic traits that differed among the treeline populations. Most genes were identified in the drought-limited site, indicating comparatively strong selection pressure of drought-tolerant phenotypes. Contrasting patterns of drought-associated genes among sampled sites and in comparison to Canadian populations in a previous study suggest that drought adaptation acts on a local scale. Our results highlight genes that are associated with wood traits which in turn are critical for the establishment and persistence of future forests under climate change.


Carotenoid-chlorophyll energy transfer in the fucoxanthin-chlorophyll complex binding a fucoxanthin acyloxy derivative.
The fucoxanthin-chlorophyll a protein from Emiliania huxleyi (E-FCP) is a member of the LHC family of light-harvesting proteins. It has a rather unusual pigment composition as its binds more Chl-c than Chl-a, and 19'-hexanoyloxyfucoxanthin (hFx) as the main carotenoid instead of fucoxanthin (Fx) typically found in various FCP complexes. The presence of a hexanoyloxy tail in hFx suppresses the charge transfer character of the S1/ICT state resulting in almost no effect of polarity on the excited state dynamics of hFx, strongly contrasting with the excited-state properties of Fx. Here we report on the dynamics of the energy transfer between hFx and Chl in E-FCP, and we compare it with Fx-Chl energy transfer in the FCP complex from Phaeodactylum tricornutum. In both complexes, the excited hFx (Fx) transfers energy from the S2 state with a sub-100 fs time constant and no effect of the hexanoyloxy tail on the efficiency of the S2 route was found. The energy transfer via the S1/ICT state has in E-FCP two channels characterized by 1.5 and 11 ps time constants, while for FCP these two channels operate with time constants of 0.8 and 4.5 ps. Thus, minimizing the charge transfer character of S1/ICT in hFx results in about twice slower energy transfer via the S1/ICT state, underlining the importance of the ICT state in facilitating carotenoid-Chl energy transfer in systems utilizing keto carotenoids as energy donors.


A Comparative Study of Left Atrial Function Index of Hypertensive Heart Failure Patients Versus Controls in a Teaching Hospital, Sub-Saharan Africa.
The left atrium contributes significantly to the left ventricular filling as it functions as a reservoir, conduit, and pump. These functions are referred to as the phasic function of the left atrium and they are assessed using left atrial volumes. The left atrial function index on the other hand is a rhythmic independent composite index which is a better marker of left atrial function. The study therefore aimed at comparing left atrial function (using the left atrial function index) among hypertensive heart failure patients, patients with hypertension but not in heart failure, and normotensive patients. The study was a cross-sectional analytical study that was carried out at Delta State University Teaching Hospital, Nigeria. A total of 80 hypertensive heart failure patients, 80 hypertensive, and 40 normotensive patients who met the inclusion criteria were recruited from the cardiology clinics using the convenience sampling method. The left atrial function index was determined using the volumetric method. Significance was assessed at p < 0.05. The left atrial function index (21.13 ± 8.83 versus 42.28 ± 10.40 versus 50.47 ± 14.37, p = 0.001) of the hypertensive heart failure group was significantly lowest when compared with the hypertensive (p < 0.001) and normotensive (p < 0.001) groups. Although the left atrial function index of the hypertensive group (42.28 ± 10.40) was lower than the normotensive group (50.47 ± 14.37), it was however not found to be significant (p = 0.12). Also, the left atrial function index was significantly (p = 0.001) worse among the patients with heart failure with reduced ejection fraction (13.5 ± 5.94) compared to heart failure with preserved ejection fraction (40.81 ± 12.12). Left atrial function index was lowest among hypertensive heart failure patients compared with hypertensive and normotensive cohorts, and it was worse among heart failure with reduced ejection fraction patients. However, there was no significant difference between the left atrial function index of the hypertensive and normotensive groups. As a result, we recommend that the left atrial function index should be incorporated into the routine echocardiographic assessment of patients in our day-to-day clinical practice and large studies should be carried out to determine the cut-off value for the left atrial function.


Open access resources for genome-wide association mapping in rice.
Increasing food production is essential to meet the demands of a growing human population, with its rising income levels and nutritional expectations. To address the demand, plant breeders seek new sources of genetic variation to enhance the productivity, sustainability and resilience of crop varieties. Here we launch a high-resolution, open-access research platform to facilitate genome-wide association mapping in rice, a staple food crop. The platform provides an immortal collection of diverse germplasm, a high-density single-nucleotide polymorphism data set tailored for gene discovery, well-documented analytical strategies, and a suite of bioinformatics resources to facilitate biological interpretation. Using grain length, we demonstrate the power and resolution of our new high-density rice array, the accompanying genotypic data set, and an expanded diversity panel for detecting major and minor effect QTLs and subpopulation-specific alleles, with immediate implications for rice improvement.


Transport of Low-Density Lipoprotein Into the Blood Vessel Wall During Atherogenic Diet in the Isolated Rabbit Carotid Artery.
Atherosclerosis is a chronic fibroproliferative disease that includes accumulation of cholesterol-rich lipids in the arterial wall. Though numerous studies have investigated atherosclerosis, not enough is known about the exact mechanisms of low-density lipoprotein (LDL) transport into the blood vessel wall. Therefore, we explored the (125)I-LDL transport into the arterial wall under constant perfusion flow and pressure as well as the influence of duration of atherogenic diet on (125)I-LDL transport and biomechanical properties of carotid artery. The isolated segment of rabbit carotid artery was used under constant perfusion flow and pressure-induced (0 mmHg and 140 mmHg) blood vessel distension, with the possibility to change and precisely calculate shear stress during the experiment. Obtained results indicate the influence of atherogenic diet duration and consequent variation of shear stress on (125)I-LDL transport into the blood vessel wall. (125)I-LDL transport into the blood vessel wall at low pressure-induced blood vessel distension decreases by the increase of the shear stress and in relation to the atherogenic diet duration. At high pressure-induced blood vessel distension, (125)I-LDL transport increases in relation to the atherogenic diet duration and the increase of shear stress. The influence of shear stress is a more dominant parameter on LDL uptake at low pressure-induced blood vessel distension; however, the atherogenic diet duration has more of a dominant influence on LDL uptake at high pressure-induced vessel distension.


Organellar DNA continues to provide a rich source of information in the genomics era.
The genomics revolution continues to change how ecologists and evolutionary biologists study the evolution and maintenance of biodiversity. It is now easier than ever to generate large molecular data sets consisting of hundreds to thousands of independently evolving nuclear loci to estimate a suite of evolutionary and demographic parameters. However, any inferences will be incomplete or inaccurate if incorrect taxonomic identities and perpetuated throughout the analytical pipeline. Due to decades of research and comprehensive online databases, sequencing and analysis of mitochondrial DNA (mtDNA), chloroplast DNA (cpDNA) and select nuclear genes can provide researchers with a cost effective and simple means to verify the species identity of samples prior to subsequent phylogeographic and population genomic analysis. The addition of these sequences to genomic studies can also shed light on other important evolutionary questions such as explanations for gene tree-species tree discordance, species limits, sex-biased dispersal patterns, adaptation, and mtDNA introgression. Although the mtDNA and cpDNA genomes often should not be used exclusively to make historical inferences given their well-known limitations, the addition of these data to modern genomic studies adds little cost and effort while simultaneously providing a wealth of useful data that can have significant implications for both basic and applied research.


Is it useful to ask "Está deprimido?" ("Are you depressed?") to terminally-ill Portuguese patients? Results from outpatient research.
Depression is a serious psychological problem in the palliative care setting. Brief screening tools for depression are lacking and need to be brief and acceptable. This study aimed to identify the properties of the single Portuguese question "Está deprimido?" ("Are you depressed?") to screen for depression. Retrospective study from 100 patient's medical records identifying the answers on the single Portuguese question for depression "Está deprimido?" ("Are you depressed?") and the HADS depression sub-scale, using a score ≥11 on the latter as the gold standard for clinically significant depressive symptoms. Sensitivity, specificity, positive predictive and negative values were calculated. Response rate for the single Portuguese question for depression was 100%. Prevalence of depression symptoms (HADS-d ≥ 11) was 43%. To the question "Está deprimido?" 60 patients responded "yes." Sixteen patients who replied "no" to the single question had clinically significant depressive symptoms based on the HADS depression sub-scale. The single tool had 65.2% sensitivity, 49.2% specificity and 50.0% and 64.4% of positive predictive and negative values, respectively. In this first preliminary retrospective Portuguese study, the single question for depression has shown poor screening properties. Future research in larger and mixed patientś samples of Portuguese terminally ill is necessary to find more accurate and robust properties of this brief tool.


Parental response to the introduction of a vaccine against human papilloma virus.
The introduction of a vaccine against human papillomavirus (HPV), a sexually transmitted virus that is the causal factor of at least 95% of invasive cervical cancer, could significantly reduce the number of cases of cervical cancer occurring in the UK each year. To ensure that individuals are protected before onset of sexual activity, it is likely that the vaccine will be offered to children around 10 years of age. It is important that parents' attitudes to HPV vaccination are taken into account, particularly as the subject relates to sexual health issues. In order to gauge parents' initial responses to the addition of HPV vaccine to the immunisation programme and identify the issues needing further research, in-depth interviews were held with parents of girls and boys aged 8-10 years. Our results show that most parents have not heard of HPV and were not aware of the role of HPV in cervical cancer. There were concerns about offering a vaccine that protects against a sexually transmitted infection to children and that the vaccine should be offered at an older age in conjunction with a sex education program. In order to avoid rejection of this vaccine, work needs to take place now to raise awareness of HPV as a cause of cervical cancer prior to any introduction of the vaccination program.


Clinical and pathological characteristics, and prognostic factors for gastric cancer survival in 155 patients in Bulgaria.
Almost one million new cases of gastric cancer were estimated to have occurred in 2012, making it the fifth most common malignancy in the world. It is also the third leading cause of cancer death of people of both genders worldwide. The aim of this study is to evaluate the significance of some prognostic factors for gastric cancer survival in 155 patients treated at Aleksandrovska University Hospital, Sofia, Bulgaria. This retrospective study includes patients diagnosed and treated at Department of Surgery of Aleksandrovska University Hospital for the 9-years period of time between January 2005 and December 2013. We classified the prognostic factors as patient-related (age at diagnosis specification, gender, and blood type), tumor-related (N-stage, tumor differentiation, process localization), and treatment related (patients who had radical surgery and adjuvant therapy). We found that blood type is the only statistically significant prognostic factor for overall survival from the patients-related group of factors (p = 0.030). The only prognostic factor from the ones in the tumor related group remains the N-stage according to the TNM classification (p = 0.003). Adjuvant could not prove its value for overall survival (p = 0.675).


Preparation of N-Graphdiyne Nanosheets at Liquid/Liquid Interface for Photocatalytic NADH Regeneration.
Two-dimensional (2D) N-graphdiyne (N-GDY) nanosheets containing different number of N were synthesized by polymerization of triazine, pyrazine, and pyridine-based monomers at liquid/liquid interface. The configurations and nanostructures of N-GDY were well-characterized. The wettability changed to more hydrophilic as the N contents increased. The collected N-GDY was further employed as metal-free photocatalyst for NADH regeneration. The catalytic performance was related with the N content in the graphdiyne. The N3-GDY demonstrated the best activity. This strategy provided a new promising platform of designing unique 2D N-GDY with tunable performance in biorelated catalysis.


Apps and wearables for monitoring physical activity and sedentary behaviour: A qualitative systematic review protocol on barriers and facilitators.
Monitoring of physical activity and sedentary behaviours by mobile phone applications (apps) and wearable technology (wearables) may improve these health behaviours. This systematic review aims to synthesise the qualitative literature on the barriers and facilitators of using apps and wearables for monitoring physical activity and/or sedentary behaviour in adults. This review protocol is registered in PROSPERO (CRD42017070194). Scientific databases including CINAHL Complete, MEDLINE, PsycINFO, SPORTDiscus, Cochrane Library and Scopus will be searched for relevant studies published from 1 January 2012 to the date the searches are conducted. Studies will be included if they incorporated adults who used an app or wearable for monitoring physical activity and/or sedentary behaviour; explored the barriers and/or facilitators of using an app and/or wearable; and were published in English. Following duplicate screening of titles and abstracts, full texts of potentially eligible papers will be screened to identify studies using qualitative approaches to explore barriers and facilitators of using apps and/or wearables for monitoring physical activity and/or sedentary behaviour. Discrepancies will be resolved through consensus or by consulting a third screener. Relevant excerpts (quotes and text) from the included papers will be extracted and analysed thematically. The Critical Appraisal Skills Programme Qualitative Research Checklist will be used to appraise included studies. The results of this work will be useful for those intending to monitor physical activity and/or sedentary behaviour using these technologies.


Fluorescent photochemical surface labeling of intact human erythrocytes.
A photolabile nitrene precursor, 3-azido-(2,7)-naphthalene disulfonate (ANDS), has been synthesized and used as a membrane-impermeable probe. The aryl azide was nonfluorescent. When activated by light, a highly reactive nitrene was generated which was capable of nonspecific covalent modifications of hydrophilic regions of cell surfaces. The products of the photolysis were highly fluorescent and modified proteins could be identified by their characteristic fluorescence after electrophoresis on sodium dodecyl sulfate polyacrylamide gels. When intact human erythrocytes were labeled with ANDS, Protein 3, the major membrane protein, and the sialoglycoproteins were modified. No proteins of apparent molecular weight greater than Protein 3 were labeled by ANDS, suggesting that none of these membrane components was exposed to the hydrophilic external surface of the red blood cell. When open erythrocyte stroma were labeled with ANDS, virtually all protein bands detectable by Coomassie blue staining could be shown to contain some fluorescence label. The significance of these findings are discussed with relation to the use of various aryl azides as surface labels of membranes.


Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis.
Objective: To determine whether prenatal cannabis use alone increases the likelihood of fetal and neonatal morbidity and mortality. Study Design: We searched bibliographic databases, such as PubMed, Embase, Scopus, Cochrane reviews, PsycInfo, MEDLINE, Clinicaltrials.gov, and Google Scholar from inception through February 14, 2022. Cohort or case-control studies with prespecified fetal or neonatal outcomes in pregnancies with prenatal cannabis use. Primary outcomes were preterm birth (PTB; <37 weeks of gestation), small-for-gestational-age (SGA), birthweight (grams), and perinatal mortality. Two independent reviewers screened studies. Studies were extracted by one reviewer and confirmed by a second using a predefined template. Risk of bias assessment of studies, using the Newcastle-Ottawa Quality Assessment Scale, and Grading of Recommendations Assessment, Development, and Evaluation for evaluating the certainty of evidence for select outcomes were performed by two independent reviewers with disagreements resolved by a third. Random effects meta-analyses were conducted, using adjusted and unadjusted effect estimates, to compare groups according to prenatal exposure to cannabis use status. Results: Fifty-three studies were included. Except for birthweight, unadjusted and adjusted meta-analyses had similar results. We found very-low- to low-certainty evidence that cannabis use during pregnancy was significantly associated with greater odds of PTB (adjusted odds ratio [aOR], 1.42; 95% confidence interval [CI], 1.19 to 1.69; I2, 93%; p=0.0001), SGA (aOR, 1.76; 95% CI, 1.52 to 2.05; I2, 86%; p<0.0001), and perinatal mortality (aOR, 1.5; 95% CI, 1.39 to 1.62; I2, 0%; p<0.0001), but not significantly different for birthweight (mean difference, -40.69 g; 95% CI, -124.22 to 42.83; I2, 85%; p=0.29). Because of substantial heterogeneity, we also conducted a narrative synthesis and found comparable results to meta-analyses. Conclusion: Prenatal cannabis use was associated with greater odds of PTB, SGA, and perinatal mortality even after accounting for prenatal tobacco use. However, our confidence in these findings is limited. Limitations of most existing studies was the failure to not include timing or quantity of cannabis use. This review can help guide health care providers with counseling, management, and addressing the limited existing safety data. Protocol Registration: PROSPERO CRD42020172343.


HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation.
Varying HLA allele-specific expression levels are associated with human diseases, such as graft versus host disease (GvHD) in hematopoietic stem cell transplantation (HSCT), cytotoxic T cell response and viral load in HIV infection, and the risk of Crohn's disease. Only recently, RNA-based next generation sequencing (NGS) methodologies with accompanying bioinformatics tools have emerged to quantify HLA allele-specific expression replacing the quantitative PCR (qPCR) -based methods. These novel NGS approaches enable the systematic analysis of the HLA allele-specific expression changes between individuals and between normal and disease phenotypes. Additionally, analyzing HLA allele-specific expression and allele-specific expression loss provide important information for predicting efficacies of novel immune cell therapies. Here, we review available RNA sequencing-based approaches and computational tools for NGS to quantify HLA allele-specific expression. Moreover, we explore recent studies reporting disease associations with differential HLA expression. Finally, we discuss the role of allele-specific expression in HSCT and how considering the expression quantification in recipient-donor matching could improve the outcome of HSCT.


Computed tomography-based surgical strategy for total anomalous pulmonary venous connection.
We used computed tomographic angiography (CTA)-based surgical planning to clarify the anatomical indications of sutureless repair technique for total anomalous pulmonary venous connection. The mid-term impact of the current surgical strategies was evaluated. One hundred twelve patients underwent repair for total anomalous pulmonary venous connection. The study period was divided into era 1 (1996-2010, n = 56) and era 2 (2011-2018, n = 56). Patients with single ventricular heart (SVH) were included. In era 2, the indications for primary sutureless repair and branch pulmonary vein incision were based on CTA findings. For patients with biventricular heart, the 5-year survival was 69% and 97% in eras 1 and 2, respectively (P = 0.0024). For patients with SVH, the 5-year survival was 21% and 70% in eras 1 and 2, respectively (P = 0.0007). During the follow-up period, the evidence of post-repair pulmonary vein stenosis (PVS) was observed in 12 patients with biventricular heart [era 1, 8 patients (23%); era 2, 4 patients (13%)], and 14 patients with SVH [era 1, 6 patients (60%); era 2, 8 patients (36%)]. Using multivariable analysis, preoperative CTA was associated with improved survival in both biventricular heart and SVH and associated with post-repair PVS-free survival in SVH. Since 2011, 12 patients with post-repair PVS underwent multiple reintervention with 1 recorded death (5-year survival: 88%). CTA-based surgical strategy for total anomalous pulmonary venous connection provided significant survival benefit. Although post-repair PVS could occur in era 2, aggressive reintervention appeared to be associated with improved survival and vein patency.


Recurrent polyposis nasi. Documentation.
After a short historical review a proposal is made for the definition of nasal polyposis. The authors studied 350 CT-scans of patients with nasal complaints. In a high percentage anatomical anomalies were observed. In 57.5% of the CT-scans sinus mucosal disease was visible. In all patients with maxillary sinus disease polyps (rounded structures) could be found; in 31% these polyps were mainly of grade 2. From a retrospective study of 111 biopsies of nasal polyposis (65 patients) it became clear that different polyps from the same patient showed substantial difference in cellular content, i.e. presence of eosinophils, neutrophils, plasma cells, glands, ducti and thickening of the basal membrane. As oral acetylsalicylic acid provocation may be hazardous in ASA-sensitive patients, the authors developed a nasal aspirin provocation test. This nasal ASA test was carried out in 10 normal test subjects, 10 patients with aspecific hyperreactivity, 10 atopic patients and 16 patients with polyposis nasi. The reproducibility of the test, however, was so poor that the nasal ASA challenge test in its present form does not appear to be of any great clinical value. Finally, the authors discuss the physiopathology of nasal polyposis.


Structural, magnetic, EPR, and electrochemical characterizations of a spin-frustrated trinuclear Cr(III) polyoxometalate and study of its reactivity with lanthanum cations.
The asymmetric Cr(III) polyoxometalate complex Cs(10)[(gamma-SiW(10)O(36))(2)(Cr(OH)(H(2)O))(3)] x 17 H(2)O (1) has been synthesized in water under atmospheric pressure from the trinuclear precursor [Cr(3)(CH(3)COO)(7)(OH)(2)] and the divacant ligand [gamma-SiW(10)O(36)](8-). Complex 1 is built up of two [gamma-SiW(10)O(36)](8-) Keggin units sandwiching a trinuclear {(Cr(III)(OH)(H(2)O))(3)} fragment where the paramagnetic centers are bridged by three mu-OH ligands forming a nearly isosceles triangle. The magnetic properties of this spin-frustrated system have thus been interpreted considering a 2-J Hamiltonian showing that the Cr(III) ions are antiferromagnetically coupled and that 1 possesses an S = 3/2 ground state with an S = 1/2 first excited state located at 11 cm(-1). These results have been confirmed by EPR spectroscopy measurements (Q-band), which have also enabled the quantification of the electronic parameters characterizing the quadruplet spin ground state. The magnitude of the magnetic exchange interactions and the nature of the ground state are discussed in light of previously reported isosceles triangular S = 3/2 clusters. UV-visible and electrochemical studies have shown that 1 is stable in aqueous media in a 1-7 pH range. This stability is chemically confirmed by the study of the reactivity of 1 with La(III) cations, which has allowed the isolation of the Cs(4)[(gamma-SiW(10)O(36))(2)(Cr(OH)(H(2)O))(3)(La(H(2)O)(7))(2)] x 20 H(2)O compound (2). Indeed, during the synthetic process of this 3d-4f system, the integrity of the [(gamma-SiW(10)O(36))(2)(Cr(OH)(H(2)O))(3)](10-) building unit constituting 1 is maintained despite the high oxophilic character of the La(III) ions. The single crystal X-ray diffraction study of 2 has revealed that in the solid state the rare earth cations connect these subunits, affording a 3d-4f double-chain monodimensional system.


Total Saponin from Root of Actinidia valvata Dunn Inhibits Hepatoma 22 Growth and Metastasis In Vivo by Suppression Angiogenesis.
The root of Actinidia valvata dunn has been widely used in the treatment of hepatocellular carcinoma (HCC), proved to be beneficial for a longer and better life in China. In present work, total saponin from root of Actinidia valvata Dunn (TSAVD) was extracted, and its effects on hepatoma H22-based mouse in vivo were observed. Primarily transplanted hypodermal hepatoma H22-based mice were used to observe TSAVD effect on tumor growth. The microvessel density (MVD), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) are characterized factors of angiogenesis, which were compared between TSAVD-treated and control groups. Antimetastasis effect on experimental pulmonary metastasis hepatoma mice was also observed in the study. The results demonstrated that TSAVD can effectively inhibit HCC growth and metastasis in vivo, inhibit the formation of microvessel, downregulate expressions of VEGF and bFGF, and retrain angiogenesis of hepatoma 22 which could be one of the reasons.


Genome-wide phylogenetic analysis of the pathogenic potential of Vibrio furnissii.
We recently reported the genome sequence of a free-living strain of Vibrio furnissii (NCTC 11218) harvested from an estuarine environment. V. furnissii is a widespread, free-living proteobacterium and emerging pathogen that can cause acute gastroenteritis in humans and lethal zoonoses in aquatic invertebrates, including farmed crustaceans and molluscs. Here we present the analyses to assess the potential pathogenic impact of V. furnissii. We compared the complete genome of V. furnissii with 8 other emerging and pathogenic Vibrio species. We selected and analyzed more deeply 10 genomic regions based upon unique or common features, and used 3 of these regions to construct a phylogenetic tree. Thus, we positioned V. furnissii more accurately than before and revealed a closer relationship between V. furnissii and V. cholerae than previously thought. However, V. furnissii lacks several important features normally associated with virulence in the human pathogens V. cholera and V. vulnificus. A striking feature of the V. furnissii genome is the hugely increased Super Integron, compared to the other Vibrio. Analyses of predicted genomic islands resulted in the discovery of a protein sequence that is present only in Vibrio associated with diseases in aquatic animals. We also discovered evidence of high levels horizontal gene transfer in V. furnissii. V. furnissii seems therefore to have a dynamic and fluid genome that could quickly adapt to environmental perturbation or increase its pathogenicity. Taken together, these analyses confirm the potential of V. furnissii as an emerging marine and possible human pathogen, especially in the developing, tropical, coastal regions that are most at risk from climate change.


Fluorine Effects on Group Migration via a Rhodium(V) Nitrenoid Intermediate.
An unprecedented rhodium(III)-catalyzed hydroarylation of α,α-difluoromethylene alkynes with N-pivaloxyl aroylamides through sequential C-H activation and aryl migration is detailed herein. A large array of α,α-difluoromethylene alkynes and N-pivaloxyl aryl amides were amenable to this transformation, thus providing a novel synthetic protocol for the construction of difluorinated 2-alkenyl aniline derivatives in high yields and with excellent regioselectivity. Notably, unique fluorine effects were found to underlie the thus unconventional reaction manifold.


A New Method for Dispersing Pristine Carbon Nanotubes Using Regularly Arranged S-Layer Proteins.
Homogeneous and stable dispersions of functionalized carbon nanotubes (CNTs) in aqueous solutions are imperative for a wide range of applications, especially in life and medical sciences. Various covalent and non-covalent approaches were published to separate the bundles into individual tubes. In this context, this work demonstrates the non-covalent modification and dispersion of pristine multi-walled carbon nanotubes (MWNTs) using two S-layer proteins, namely, SbpA from Lysinibacillus sphaericus CCM2177 and SbsB from Geobacillus stearothermophilus PV72/p2. Both the S-layer proteins coated the MWNTs completely. Furthermore, it was shown that SbpA can form caps at the ends of MWNTs. Reassembly experiments involving a mixture of both S-layer proteins in the same solution showed that the MWNTs were primarily coated with SbsB, whereas SbpA formed self-assembled layers. The dispersibility of the pristine nanotubes coated with SbpA was determined by zeta potential measurements (-24.4 +/- 0.6 mV, pH = 7). Finally, the SbpA-coated MWNTs were silicified with tetramethoxysilane (TMOS) using a mild biogenic approach. As expected, the thickness of the silica layer could be controlled by the reaction time and was 6.3 +/- 1.25 nm after 5 min and 25.0 +/- 5.9 nm after 15 min. Since S-layer proteins have already demonstrated their capability to bind (bio)molecules in dense packing or to act as catalytic sites in biomineralization processes, the successful coating of pristine MWNTs has great potential in the development of new materials, such as biosensor architectures.


A novel cervical dilatation force measurement instrument.
A simple and robust instrument for cervical dilatation force measurement is described which measures axial insertion force but is not affected by lateral loads. The instrument is battery-powered, self-contained and displays actual axial force and peak axial force on digital liquid crystal displays.


Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease.
Trypanosoma cruzi the cause of Chagas disease persists in tissues of infected experimental animals and humans. Here we demonstrate the persistence of the parasite in adipose tissue from of three of 10 elderly seropositive patients with chronic chagasic heart disease. Nine control patients had no parasites in the fat. We also demonstrate that T. cruzi parasitizes primary adipocytes in vitro. Thus, in humans as in mice the parasite may persist in adipose tissue for decades and become a reservoir of infection.


Single Point Mutations in Pediatric Differentiated Thyroid Cancer.
Differentiated thyroid cancer (DTC) is rare in children. Previous studies have suggested that it has different clinicopathologic features and mutation profiles compared with adult DTC. However, those studies focused on a single or limited number of gene mutations. This study comprehensively investigated a large series of pediatric DTC for single point mutations in BRAF, HRAS, KRAS, NRAS, PIK3CA, PTEN, and TERT. It also analyzed associations between clinicopathologic features and the BRAFV600E mutation. Eighty-nine consecutive cases seen in children and adolescents (≤18 years) during 1998-2015 were identified. Rare variants of DTC were excluded, and the study focused on 72 (91.1%) classical papillary thyroid carcinoma (PTC) and seven (8.9%) follicular variant PTC. These included 68 (86.1%) females and 11 (13.9%) males, with a median age of 15.5 years (range 8-18 years). The clinical and histopathological data were obtained from medical records. DNA was extracted from paraffin-embedded tumor tissue, and was PCR-amplified and directly sequenced. Mutations detected included BRAFV600E in 19/72 (26.4%) classical PTC samples, and in none of seven follicular variant PTC. Other mutations included: 1/78 (1.3%) successfully amplified tumor samples with TERT C228T; 2/79 (2.5%) NRAS 61 (c.181C>A and c.182A>G); 1/73 (1.4%) PIK3CA exon 9 (c.1589A>G and c.1598C>T in one tumor); 1/79 (1.3%) PIK3CA exon 20 (c.2951G>A); and 1/74 (1.4%) PTEN exon 5 (c.295G>A). No mutation was found in HRAS, KRAS, NRAS12, PTEN exons 6, 7, and 8, and TERT C250T. No significant association was found between BRAFV600E mutation and sex, extrathyroidal invasion, tumor multifocality, vascular invasion, lymph node or distant metastases, and persistent/recurrent disease. In pediatric DTC, the prevalence of the BRAFV600E mutation is significantly less common compared with adult DTC, and there is no association between this mutation and the histopathological features and outcome of PTC. PIK3CA, PTEN, NRAS 61, and TERT C228T mutations are rare.


The Weighting of Cues to Upright Following Stroke With and Without a History of Pushing.
Perceived upright depends on three main factors: vision, graviception, and the internal representation of the long axis of the body. We assessed the relative contributions of these factors in individuals with sub-acute and chronic stroke and controls using a novel tool; the Oriented Character Recognition Test (OCHART). We also considered whether individuals who displayed active pushing or had a history of pushing behaviours had different weightings than those with no signs of pushing. Three participants experienced a stroke 6 months prior: eight with a history of pushing. In total, 12 participants served as healthy aged-matched controls. Visual and graviceptive cues were dissociated by orienting the visual background left, right, or upright relative to the body, or by orienting the body left, right, or upright relative to gravity. A three-vector model was used to quantify the weightings of vision, graviception, and the body to the perceptual upright. The control group showed weightings of 13% vision, 25% graviception, and 62% body. Some individuals with stroke showed a similar pattern; others, particularly those with recent stroke, showed different patterns, for example, being unaffected by one of the three factors. The participant with active pushing behaviour displayed an ipsilesional perceptual bias (>30°) and was not affected by visual cues to upright. The results of OCHART may be used to quantify the weightings of multisensory inputs in individuals post-stroke and may help characterize perceptual sources of pushing behaviours.


Cellular Models for the Study of Prions.
It is now established that numerous amyloid proteins associated with neurodegenerative diseases, including tau and α-synuclein, have essential characteristics of prions, including the ability to create transmissible cellular pathology in vivo. We have developed cellular bioassays that report on the various features of prion activity using genetic engineering and quantitative fluorescence-based detection systems. We have exploited these biosensors to measure the binding and uptake of tau seeds into cells in culture and to quantify seeding activity in brain samples. These cell models have also been used to propagate tau prion strains indefinitely in culture. In this review, we illustrate the utility of cellular biosensors to gain mechanistic insight into prion transmission and to study neurodegenerative diseases in a reductionist fashion.


Micro-analytical evidence of origin and degradation of copper pigments found in Bohemian Gothic murals.
Correct identification of pigments and all accompanying phases found in colour layers of historical paintings are relevant for searching their origin and pigment preparation pathways and for specification of their further degradation processes. We successfully applied the analytical route combining non-destructive in situ X-ray fluorescence analyses with subsequent laboratory investigation of micro-samples by optical microscopy, scanning electron microscopy/energy-dispersive spectroscopy and X-ray powder micro-diffraction (micro-XRD) to obtain efficiently all the data relevant for mineralogical interpretations of the copper pigments origin. Cu salts (carbonates, chlorides, sulphates, etc.) used as pigments exist in a range of polymorphs with similar or identical composition. The efficiency of the micro-XRD for direct identification of such crystal phases present in micro-samples of colour layers was demonstrated in the presented paper. A new, until now unpublished, type of copper pigment--cumengeite, Pb(21)Cu(20)Cl(42)(OH)(40)--used as a blue pigment on a sacral wall painting in the Czech Republic was found by means of micro-XRD. Furthermore, azurite, malachite, paratacamite, atacamite and posnjakite were identified in fragments of colour layers of selected Gothic wall paintings. We found Cu-Zn arsenates indicating the natural origin of azurite and malachite; artificial malachite was distinguishable according to its typical spherulitic crystals. The corrosion of blue azurite to green basic Cu chloride was clearly evidenced on some places exposed to the action of salts and moisture-in a good agreement with the results of laboratory experiments, which also show that oxalic acid accelerates the corrosion of Cu pigments.


The Portrait of Cyberchondria-A Cross-Sectional Online Study on Factors Related to Health Anxiety and Cyberchondria in Polish Population during SARS-CoV-2 Pandemic.
The SARS-CoV-2 pandemic has served as a magnifying glass for cyberchondria, while the internet emerged as one of the main sources of medical information and support. The core ambition of this study was to estimate the level of cyberchondria and describe the socio-demographic, clinical and pandemic-related factors affecting its severity amid the SARS-CoV-2 pandemic. A cross-sectional study was performed between 16 May 2020 and 29 December 2020 in Poland within a sample of 538 adult internet users. The online survey tool included a Polish adaptation of the Cyberchondria Severity Scale (CSS-PL) and the Short Health Anxiety Inventory (SHAI), complemented with a set of questions covering sociodemographic, clinical and pandemic-related factors. Participants were clustered according to severity of health anxiety and cyberchondria symptoms. The performed binary logistic regression indicated professional inactivity, having a chronic mental disorder and subjectively limited access to healthcare due to COVID-19 to be key determinants of severe health anxiety and cyberchondria. Cyberchondria might be a remarkable public health issue as large proportion of respondents from the analyzed sample population of internet users met the criteria for severe symptoms. Key determinants of intense cyberchondria corresponded with employment stability, mental resilience and accessibility of healthcare services, which could be greatly challenged amid the pandemic.


Natural history of peripheral neovascularisation in diabetic retinopathy.
A study of 62 untreated eyes of 54 diabetic patients with peripheral neovascularisation is reported. The study shows that neovascularisation rarely remains confined to one sector of the retina; 18% of eyes had developed disc new vessels within one year, 27% had a vitreous haemorrhage within five years, and 10% developed either macular traction or a retinal detachment.


Ventilation and neuromuscular blocking drugs.
Ventilatory failure after administration of neuromuscular blocking agents is an important factor in anaesthesia-related perioperative morbidity and mortality. Improved knowledge and new monitoring methods may avoid ventilatory failure caused by incomplete recovery of neuromuscular function in the postoperative period. Central respiratory muscles are less sensitive than, and their time course of neuromuscular block is different from those of, pharyngeal muscles and those of the upper airway. Differences in potency and time course of neuromuscular block may lead to incorrect assessment of ventilatory function during onset and recovery. Even if recovery of the mechanical adductor pollicis train-of-four (TOF) response to a ratio of 0.70 has previously been associated with adequate ventilatory capacity, it is now shown that hypoxic ventilatory responses may be markedly reduced despite adequate respiratory force at a TOF ratio of 0.70. Hence, partial paralysis may interfere with ventilatory regulation in hypoxaemia. Consequently, monitoring neuromuscular function by peripheral nerve stimulation in one muscle yields limited information about total ventilatory capacity, especially the function of the upper airway and ventilatory regulation. Therefore, neuromuscular monitoring should be used with caution during recovery and should always be combined with bedside clinical tests if possible.


Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-one (TIBO) derivatives.
A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin- 2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products. A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group. The best analogue, 9jj, inhibited HIV-1 with an IC50 of 4 microM, which is comparable to the activity level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials as an anti-AIDS therapy.


Establishing a Stable Anode-Electrolyte Interface in Mg Batteries by Electrolyte Additive.
Simple magnesium salts with high electrochemical and chemical stability and adequate ionic conductivity represent a new-generation electrolyte for magnesium (Mg) batteries. Similar to other Mg electrolytes, the simple-salt electrolyte also suffers from high charge-transfer resistance on the Mg surface due to the adsorbed species in the solution. In the current study, we built a model Mg cell system with the Mg[B(hfip)4]2/DME electrolyte and Chevrel phase Mo6S8 cathode, to demonstrate the effect of such anode-electrolyte interfacial properties on the full-cell performance. It was found that the cell required additional activation cycles to achieve its maximal capacity. The activation process is mainly attributed to the conditioning of the anode-electrolyte interface, which could be boosted by introducing an additive amount of Mg(BH4)2 to the Mg[B(hfip)4]2/DME electrolyte. Electrochemical and spectroscopic analyses revealed that the Mg(BH4)2 additive helps to remove the native oxide layer and promotes the formation of a solid electrolyte interphase layer on Mg. As a result, the full cell with the additive-containing electrolyte delivered a stable capacity from the second cycle onward. Further battery tests showed a reversible cycling for 600 cycles and an excellent rate capability, indicating good compatibility of the Mg(BH4)2 additive. The current study not only provides fundamental insights into the interfacial phenomena in Mg batteries but also highlights the facile tunability of the simple-salt Mg electrolytes.


Exploring how symptoms of attention-deficit/hyperactivity disorder are related to reading and mathematics performance: general genes, general environments.
Children with attention-deficit/hyperactivity disorder (ADHD) tend to perform more poorly on tests of reading and mathematical performance than their typical peers. Quantitative genetic analyses allow for a better understanding of the etiology of ADHD and reading and mathematics outcomes, by examining their common and unique genetic and environmental influences. Analyses were conducted on a sample 271 pairs of 10-year-old monozygotic and dizygotic twins drawn from the Western Reserve Reading and Mathematics Project. In general, the results suggested that the associations among ADHD symptoms, reading outcomes, and math outcomes were influenced by both general genetic and general shared-environment factors. The analyses also suggested significant independent genetic effects for ADHD symptoms. The results imply that differing etiological factors underlie the relationships among ADHD and reading and mathematics performance. It appears that both genetic and common family or school environments link ADHD with academic performance.


Thyroxine, 3,5,3'-triiodothyronine, and 3,3',5'-triiodothyronine concentrations in several tissues of the rat: effects of amiodarone and desethylamiodarone on thyroid hormone metabolism [corrected].
The effects of amiodarone, an iodinated antiarrhythmic drug, on thyroid hormone metabolism are known. It is not known whether the main metabolite, desethylamiodarone, is responsible. We investigated the influence of both compounds on the intracellular rT3, T4, and T3 concentrations in tissues of the rat, the source of T3 (plasma-derived vs. produced locally from T4) and T3 and T4 production by the thyroid. Special attention is paid to the heart. We found that both amiodarone and desethylamiodarone cause a decrease in intracellular T3 in all tissues (P less than 0.001), in most tissues an increase in T4 and a greater increase in the rT3 concentration. Both compounds inhibit both deiodination (P less than 0.0001) and T3 production by the thyroid (P less than 0.0001); T4 production was enhanced (P less than 0.05). In the heart a hypothyroid-like state, caused by decreased plasma-derived T3 (P less than 0.0001), was found. But a pool of T3 produced locally from T4 was present (21% of the total T3, P less than 0.01), which has never been demonstrated under normal conditions. This pool might play a role in the mechanism of action of the drugs. Differences between the drugs were organ-specific, but the effects of desethylamiodarone were as strong as or stronger than those of amiodarone. We conclude that desethylamiodarone was responsible for the changes, although the possibility of a common metabolite, generated later, has not been excluded.


Ferroptosis Is Involved in Sex-Specific Small Intestinal Toxicity in the Offspring of Adult Mice Exposed to Polystyrene Nanoplastics during Pregnancy.
Nanoplastics are common contaminants in the living environment. Thus far, no investigations have focused on small intestinal injury in the offspring of adult mice that were exposed to nanoplastics through the respiratory system during pregnancy. Here, we evaluated potential intestinal injury in the offspring of adult mice that were subjected to maternal 80 nm polystyrene nanoparticle (PS-NP) exposure during gestation. PS-NP exposure significantly reduced the birth weight of female mice compared with male mice. However, the adult body weights of the female and male offspring were substantially greater in the PS-NP-exposed groups. Additionally, we found that exposure to PS-NPs during pregnancy caused histological changes in the small intestines of both female and male offspring. Mechanistic analysis revealed upregulation of reactive oxygen species in the small intestines, as indicated by changes in the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). Furthermore, exposure to PS-NPs led to downregulation of GPx4, FTH1, and FTL protein levels, indicating initiation of ferroptosis. Notably, the changes in mRNA expression levels of GPx4, FTH1, and FTL differed between female and male offspring. Although all phenotypes failed to demonstrate classic dose-dependent effects, the data imply that small intestinal toxicity is greater in female offspring than in male offspring. Our results suggest that PS-NP exposure during pregnancy causes sex-specific small intestinal toxicity, which might contribute to reactive oxygen species activation and subsequent ferroptosis. Overall, this study showed toxic effects in offspring after PS-NP exposure during pregnancy.


Enhancement of the sulfur capture capacity of limestones by the addition of Na2CO3 and NaCl.
The ability of Na2CO3 and NaCl to enhance the sulfur capture capacity of three limestones was evaluated via fixed-bed calcination and sulfation experiments. The tested limestones represent three different sulfation morphologies: unreacted-core, network, and uniformly sulfated. Treatment with aqueous or powdered Na2CO3 significantly increased the Ca-utilization for two stones which normally sulfate in an unreacted-core pattern (20% to 45%) and network pattern (33% to 49%). The increase was lower for the uniformly sulfated stone (44% to 48%). Na2CO3 treatment increased the number of macropores leading to uniform sulfation of all particles, nearly eliminating the normal strong dependence of utilization on limestone type and particle size. The effect of Na2CO3 is believed to be associated with formation of a eutectic melt which enhances ionic diffusion and accelerates molecular rearrangement of the CaO. Treatment with aqueous NaCl solution caused a decrease in utilization, probably due to formation of large grains and plugging of pores caused by formation of a large amount of eutectic melt. The effect of Na2CO3 is less sensitive than that of NaCl to the amount added and the combustion environment (temperature and gas composition). In addition, Na2CO3 neither promotes corrosion nor forms chlorinated byproducts, which are main concerns associated with NaCl. Thus, Na2CO3 appears to have significant advantages over NaCl for enhancement of limestone sulfur capture capacity in fluidized-bed combustors.


Identification of collagen-induced arthritis loci in aged multiparous female mice.
Collagen-induced arthritis in mice is one of the most commonly used autoimmune experimental models, with many similarities to rheumatoid arthritis. Since collagen-induced arthritis is a complex polygenic disease there is a need for identification of several major disease-controlling genes. Because rheumatoid arthritis particularly affects aged women, we have in the present study identified new genetic regions critical for collagen-induced arthritis by studying aged female mice of a cross between NFR/N and B10.Q (H-2q haplotype). The mice in the present study had different reproductive histories, which did not significantly affect the onset, incidence or severity of the disease. A total of 200 female mice were used in a total genome-wide screening with 125 microsatellite markers. We found one new significant quantitative trait locus affecting the arthritis incidence, severity and day of onset on chromosome 11 (denoted Cia40), which colocalizes with a locus controlling pregnancy failure. Furthermore, a quantitative trait locus of suggestive significance associated with the incidence, severity and day of onset was identified on chromosome 1. Finally, a suggestively significant quantitative trait locus associated with collagen type II antibody titers was identified on chromosome 13. This study indicates that several gene loci control arthritis in aged multiparous females, and that at least one of these loci coincides with pregnancy failure.


Outcome of pregnancy in patients with structural or ischaemic heart disease: results of a registry of the European Society of Cardiology.
To describe the outcome of pregnancy in patients with structural or ischaemic heart disease. In 2007, the European Registry on Pregnancy and Heart disease was initiated by the European Society of Cardiology. Consecutive patients with valvular heart disease, congenital heart disease, ischaemic heart disease (IHD), or cardiomyopathy (CMP) presenting with pregnancy were enrolled. Data for the normal population were derived from the literature. Sixty hospitals in 28 countries enrolled 1321 pregnant women between 2007 and 2011. Median maternal age was 30 years (range 16-53). Most patients were in NYHA class I (72%). Congenital heart disease (66%) was most prevalent, followed by valvular heart disease 25%, CMP 7%, and IHD in 2%. Maternal death occurred in 1%, compared with 0.007% in the normal population. Highest maternal mortality was found in patients with CMP. During pregnancy, 338 patients (26%) were hospitalized, 133 for heart failure. Caesarean section was performed in 41%. Foetal mortality occurred in 1.7% and neonatal mortality in 0.6%, both higher than in the normal population. Median duration of pregnancy was 38 weeks (range 24-42) and median birth weight 3010 g (range 300-4850). In centres of developing countries, maternal and foetal mortality was higher than in centres of developed countries (3.9 vs. 0.6%, P < 0.001 and 6.5 vs. 0.9% P < 0.001) The vast majority of patients can go safely through pregnancy and delivery as long as adequate pre-pregnancy evaluation and specialized high-quality care during pregnancy and delivery are available. Pregnancy outcomes were markedly worse in patients with CMP and in developing countries.


A cell-permeable fluorescent polymeric thermometer for intracellular temperature mapping in mammalian cell lines.
Changes in intracellular temperatures reflect the activity of the cell. Thus, the tool to measure intracellular temperatures could provide valuable information about cellular status. We previously reported a method to analyze the intracellular temperature distribution using a fluorescent polymeric thermometer (FPT) in combination with fluorescence lifetime imaging microscopy (FLIM). Intracellular delivery of the FPT used in the previous study required microinjection. We now report a novel FPT that is cell permeable and highly photostable, and we describe the application of this FPT to the imaging of intracellular temperature distributions in various types of mammalian cell lines. This cell-permeable FPT displayed a temperature resolution of 0.05°C to 0.54°C within the range from 28°C to 38°C in HeLa cell extracts. Using our optimized protocol, this cell-permeable FPT spontaneously diffused into HeLa cells within 10 min of incubation and exhibited minimal toxicity over several hours of observation. FLIM analysis confirmed a temperature difference between the nucleus and the cytoplasm and heat production near the mitochondria, which were also detected previously using the microinjected FPT. We also showed that this cell-permeable FPT protocol can be applied to other mammalian cell lines, COS7 and NIH/3T3 cells. Thus, this cell-permeable FPT represents a promising tool to study cellular states and functions with respect to temperature.


Clone mapper: an online suite of tools for RNAi experiments in Caenorhabditis elegans.
RNA interference (RNAi), mediated by the introduction of a specific double-stranded RNA, is a powerful method to investigate gene function. It is widely used in the Caenorhabditis elegans research community. An expanding number of laboratories conduct genome-wide RNAi screens, using standard libraries of bacterial clones each designed to produce a specific double-stranded RNA. Proper interpretation of results from RNAi experiments requires a series of analytical steps, from the verification of the identity of bacterial clones, to the identification of the clones' potential targets. Despite the popularity of the technique, no user-friendly set of tools allowing these steps to be carried out accurately, automatically, and at a large scale, is currently available. We report here the design and production of Clone Mapper, an online suite of tools specifically adapted to the analysis pipeline typical for RNAi experiments with C. elegans. We show that Clone Mapper overcomes the limitations of existing techniques and provide examples illustrating its potential for the identification of biologically relevant genes. The Clone Mapper tools are freely available via http://www.ciml.univ-mrs.fr/EWBANK_jonathan/software.html.


Hepatopulmonary syndrome associated with autoimmune liver cirrhosis.
A 46-year-old woman presented for evaluation of liver dysfunction and dyspnoea. Laboratory examination showed high levels of gamma-globulin, immunoglobulin (Ig)G, and antinuclear antibodies. Laparoscopy demonstrated hepatic cirrhosis. Despite normal spirometry, hypoxaemia (which was worse in standing position) and a low diffusing capacity were present. The shunt ratio calculated using arterial blood gas was 6.4%, but was 40% when measured using 99mTc-macroaggregated albumin scanning. The discrepancy between the ratios indicated that hypoxaemia was caused by intrapulmonary vascular dilatation. The patient was diagnosed with hepatopulmonary syndrome associated with autoimmune liver cirrhosis.


Expressional and mutational analysis of pro-apoptotic Bcl-2 member PUMA in hepatocellular carcinomas.
Deregulation of apoptosis is involved in mechanisms of cancer development. PUMA is a pro-apoptotic member of the Bcl-2 family and mediates p53-dependent and -independent apoptosis. The aim of this study was to investigate whether alterations of PUMA protein expression and somatic mutations of PUMA gene are characteristics of human hepatocellular carcinoma (HCC). We analyzed expression of PUMA protein in 20 HCCs using immunohistochemistry. Also, we analyzed mutation of the Bcl-2 homology 3 (BH3) domain of PUMA gene, which is an important domain in apoptosis function of PUMA by single-strand conformation polymorphism (SSCP) in 69 HCCs. PUMA protein expression was detected in both HCC cells and non-tumor hepatocytes in all of the 20 HCCs. In 10 of these HCCs, cancer cells showed higher PUMA expression than non-tumor (cirrhotic) hepatocytes of the same patients; whereas in the remaining 10, cancer cells and non-tumor hepatocytes showed similar levels. Mutational analysis revealed no PUMA BH3 domain mutation in the 69 HCCs, suggesting that PUMA BH3 domain mutation is not a direct target of inactivation in hepatocellular cancer development. The increased expression of PUMA in malignant hepatocellular cells relative to that in non-tumor hepatocytes suggests that PUMA expression may play a role in HCC development.


Facilitated osteogenesis of magnesium implant by coating of strontium incorporated calcium phosphate.
This study investigated the corrosion resistance and biocompatibility of magnesium coated with strontium-doped calcium phosphate (Sr-CaP) for dental and orthopedic applications. Sr-CaP was coated on biodegradable magnesium using a chemical dipping method. Magnesium coated with Sr-CaP exhibited better corrosion resistance than pure magnesium. Sr-CaP-coated magnesium showed excellent cell proliferation and differentiation. Additionally, new bone formation was confirmed in vivo. Therefore, Sr-CaP-coated magnesium with reduced degradation and improved biocompatibility can be used for orthopedic and dental implant applications.


Risk Factors for Sporadic Diffuse Lamellar Keratitis After Microkeratome Laser-Assisted In Situ Keratomileusis: A Retrospective Large Database Analysis.
To determine the factors associated with sporadic diffuse lamellar keratitis (DLK) after microkeratome laser-assisted in situ keratomileusis (LASIK). This large database retrospective study included consecutive cases of LASIK performed between 2007 and 2016 at Care-Vision Laser Centers, Tel-Aviv, Israel. Patients were divided into 2 groups according to whether or not they subsequently developed DLK. A total of 24,026 eyes of 12,013 patients with a mean age of 32.9 ± 10.3 years were included. Post-LASIK DLK developed in 464 eyes (1.9%), and the annual rate decreased from 7.1% (2007) to 1.7% (2016) (P < 0.001). The DLK group had a higher proportion of males (58.5% vs. 52.1%, P = 0.006), greater preoperative central corneal thickness (549.5 ± 32.6 vs. 545.3 ± 30.5 μm, P = 0.005), and a lower proportion of high astigmatism (>3 D) (0.4% vs. 1.6%, P = 0.05). The DLK group had a higher proportion of previous LASIK treatment (2.8% vs. 1.3%, P = 0.006), Moria M2 (rather than the SBK) microkeratome (71.1% vs. 34.0%, P < 0.001), smaller suction ring number (P < 0.001), greater stop size (P < 0.001), and greater flap thickness (119.2 ± 50.4 vs. 110.8 ± 22.2, P = 0.007). In multivariable analysis, a smaller suction ring number [odds ratio (OR) 0.89, P = 0.04], Moria M2 microkeratome (OR 5.26, P < 0.001), larger optical zone (OR = 2.04, P = 0.01), and higher spherical equivalent (OR = 1.08, P = 0.02) were associated with DLK. In the modern LASIK era, the incidence of DLK continues to decrease. Higher preoperative ametropia, smaller suction ring number, an older type of microkeratome, and larger optical zones are associated with higher DLK rates after LASIK.


The effect of different positions during non-stress test on maternal hemodynamic parameters, satisfaction, and fetal cardiotocographic patterns.
Maternal position is one of the most important factors to be considered during Non-Stress Test (NST). It should be a part of practice guidelines, where the appropriate maternal position reduces test-related errors and false-positive results. This study aimed to investigate the effect of different maternal positions during NST on maternal hemodynamic parameters, satisfaction, and fetal Cardiotocographic (CTG) pattern. A quasi-experimental research design was conducted at NST clinic, outpatient department/ Maternal and Children hospital at Najran city, Saudi Arabia. The study comprised a convenience sample of 118 low-risk pregnant women in their third trimester of pregnancy. Data was collected from January to June 2020. All women were assessed in the three different positions; supine, left lateral, and semi-fowler position concerning CTG pattern, maternal hemodynamic parameters, and satisfaction. The study results indicated a higher Fetal Heart Rate (FHR), increased accelerations, and fetal movement in the left lateral position, followed by a semi-fowler position compared to the supine position with statistically significant differences. No statistically significant differences (P>0.05) were observed regarding FHR variability and NST reactivity in the three positions. In addition, there were statistically significant differences (P <0.05) between the different maternal positions regarding maternal heart rate, systolic Blood pressure (BP), diastolic BP, and maternal satisfaction. The current study concluded that left lateral and semi- fowler positions were associated with a more favorable CTG pattern, maternal hemodynamic parameters, and satisfaction than the supine position. Left lateral and semi-fowler positions during the NST test should be standardized to reduce practical variations among health care providers, which, in turn, may reduce the need for unnecessary, expensive, and even hazardous interventions.


A Study of the Flexural Properties of PA12/Clay Nanocomposites.
Polymer nanocomposites consist of a polymer matrix and reinforcing particles that have at least one dimension under 100 nm. The processing of nanocomposite polymers is the most important stage, determining the final properties of nanocomposites. Nanocomposites are now preferentially prepared by melt-mixing using conventional compounding processes such as twin-screw extrusion. Many processing parameters (polymer matrix type, content and type of nanofiller, barrel temperature, screw speed, number and shape of extruder screws, etc.) affect the properties of nanocomposites. This research work represents an investigation of the influence of processing parameters (amount of nanoclay filler, the screw rotation speed, and extruder barrel temperature) on the flexural properties of polyamide 12/nanoclay-reinforced nanocomposite. From the test results, it is apparent that an increase in nanoclay content from 1 to 8% significantly increases flexural strength. The obtained nanocomposite has a 19% higher flexural strength and a 56% higher flexural modulus than pure PA12. Mathematical models that show the dependence of flexural strength and flexural modulus on the processing parameters used were obtained as a result of this analysis.


Language-Specific Attention Treatment for Aphasia: Description and Preliminary Findings.
The need for a specific, language-based treatment approach to aphasic impairments associated with attentional deficits is well documented. We describe language-specific attention treatment, a specific skill-based approach for aphasia that exploits increasingly complex linguistic tasks that focus attention. The program consists of eight tasks, some with multiple phases, to assess and treat lexical and sentence processing. Validation results demonstrate that these tasks load on six attentional domains: (1) executive attention; (2) attentional switching; (3) visual selective attention/processing speed; (4) sustained attention; (5) auditory-verbal working memory; and (6) auditory processing speed. The program demonstrates excellent inter- and intrarater reliability and adequate test-retest reliability. Two of four people with aphasia exposed to this program demonstrated good language recovery whereas three of the four participants showed improvements in auditory-verbal working memory. The results provide support for this treatment program in patients with aphasia having no greater than a moderate degree of attentional impairment.


HIV induces maturation of monocyte-derived dendritic cells and Langerhans cells.
In HIV infection, dendritic cells (DCs) may play multiple roles, probably including initial HIV uptake in the anogenital mucosa, transport to lymph nodes, and subsequent transfer to T cells. The effects of HIV-1 on DC maturation are controversial, with several recent conflicting reports in the literature. In this study, microarray studies, confirmed by real-time PCR, demonstrated that the genes encoding DC surface maturation markers were among the most differentially expressed in monocyte-derived dendritic cells (MDDCs), derived from human blood, treated with live or aldrithriol-2-inactivated HIV-1(BaL). These effects translated to enhanced cell surface expression of these proteins but differential expression of maturation markers was only partial compared with the effects of a conventional potent maturation stimulus. Such partially mature MDDCs can be converted to fully mature cells by this same potent stimulus. Furthermore, live HIV-1 stimulated greater changes in maturation marker surface expression than aldrithriol-2-inactivated HIV-1 and this enhanced stimulation by live HIV-1 was mediated via CCR5, thus suggesting both viral replication-dependent and -independent mechanisms. These partially mature MDDCs demonstrated enhanced CCR7-mediated migration and are also able to stimulate interacting T cells in a MLR, suggesting DCs harboring HIV-1 might prepare CD4 lymphocytes for transfer of HIV-1. Increased maturation marker surface expression was also demonstrated in native DCs, ex vivo Langerhans cells derived from human skin. Thus, HIV initiates maturation of DCs which could facilitate subsequent enhanced transfer to T cells.


[A Case of Primary Duodenal Cancer with Duodenocolic Fistula Treated with Pancreatoduodenectomy and Right Hemicolectomy].
A patient was 59-year-old female. She presented our hospital with weight loss, anorexia and lower abdominal bloating. Abdominal computed tomography(CT), gastrointestinal endoscopy, colonoscopy and duodenal fistulagram showed duodenal cancer or colon cancer with duodenocolic fistula and ovary metastasis. She underwent subtotal stomach preserving pancreatoduodenectomy and right hemicolectomy. In these pathological findings, tumor was diagnosed as a duodenal cancer with duodenocolic fistula. She was surviving 12 months after the last surgery. In cases of cancer with duodenocolic fistula, pancreatoduodenectomy with right hemicolectomy would be necessary for nutrition improvement and cancer treatment.


Groin recurrence in carcinoma of the vulva: management and outcome.
The aim of the study was to investigate the management and outcome of inguinal recurrence in vulvar carcinoma patients. A retrospective chart review was conducted on 140 patients with squamous cell carcinoma of the vulva treated between 1994 and 2006. Twenty-one patients were found to have groin recurrence. Median interval between primary treatment of vulvar cancer and groin recurrence was 7 months. Three patients refused any treatment, 3 received chemotherapy, 2 inguino-pelvic radiotherapy and 13 had resection of the groin recurrence. After surgery seven patients received irradiation of the groin and pelvis, and three patients received chemotherapy. One patient died following surgery; 19 patients died of disease with the median survival after diagnosis of inguinal recurrence of 9 months. Only one patient is alive without evidence of disease at 60 months following surgery. In univariate analysis, stage and grade at diagnosis, age and performance status at the recurrent disease, and the extent of residual tumour after resection of groin recurrence were predictors for survival. Groin recurrences from vulvar carcinoma carry a poor prognosis. Multi-modal treatment may result in a palliation of the disease, and a very limited number of patients have long-term survival.


Synchronous breast and rectal cancers in a man.
Breast cancer in men is relatively rare and its coexistence with other primary non-breast cancers exceptional. Here, we report the case of a 50-year-old man who presented with symptoms of rectal adenocarcinoma and in whom a synchronous, asymptomatic cancer of the left breast was found incidentally at physical examination.


Methodology for constructing problem definitions in bioinformatics.
A recurrent criticism is that certain bioinformatics tools do not account for crucial biology and therefore fail answering the targeted biological question. We posit that the single most important reason for such shortcomings is an inaccurate formulation of the computational problem. Our paper describes how to define a bioinformatics problem so that it captures both the underlying biology and the computational constraints for a particular problem. The proposed model delineates comprehensively the biological problem and conducts an item-by-item bioinformatics transformation resulting in a germane computational problem. This methodology not only facilitates interdisciplinary information flow but also accommodates emerging knowledge and technologies.


Pharmacokinetics of baicalin-phospholipid complex in rat plasma and brain tissues after intranasal and intravenous administration.
The aim of this study is to determine whether baicalin can be transferred along the olfactory pathway to the brain after nasal administration of baicalin phospholipid (BP) complex to rats, thereby circumventing the blood brain barrier. The concentration of baicalin in plasma and different brain tissues (olfactory bulb, cerebral cortex, striatum and cerebellum) were measured by high-performance liquid chromatography (HPLC). The ratios of the area under the concentration-time curve (AUC) values of intranasal to intravenous administrations were 54.21%, 240.59%, 374.71%, and 114.54% in plasma, cerebral cortex, striatum, and cerebellum, respectively. In the olfactory bulb, the AUC values of intranasal to intravenous administrations were 3355.4 +/- 378.8 microg/g-min versus 0 microg/g x min following intravenous administration. The ratios of AUC values of intranasal to intravenous administrations were72.75 %, 240.59 %, 374.71%, 114.54% in plasma, cortex, striatum, cerebellum respetively. The proportion of baicalin in the brain tissues from the olfactory transfer was also calculated, and the result shows that, following intranasal administration, approximately 52.36%-100% baicalin content at 8 h was transported to the brain via the olfactory pathway. In conclusion, the BP complex is transferred into the olfactory bulb via the olfactory pathway in rats, and the BP complex intranasal delivery is a promising approach to protect against cerebral ischemic injury.


Correlation between IL-28 polymorphism and spontaneous clearance in HCV patients: systematic review and meta-analysis.
Hepatitis C virus (HCV) is a serious global health issue. Nearly 20% of HCV patients spontaneously clear the virus. While some studies have shown an association of spontaneous clearance (SC) of the virus with interleukin (IL) 28B single-nucleotide polymorphisms (SNPs), others did not show such a relationship. Thus, the purpose of the present study was to investigate the association of IL28B polymorphisms (12979860 SNP) with SC of HCV infection. Upon initial screening of the databases, a total of 545 articles were retrieved, of which 22 studies that met predefined eligibility criteria were entered into the meta-analysis. Odds ratios (ORs) with confidence intervals (95% CI), heterogeneity, publication bias, and sensitivity analysis were assessed. According to the meta-analysis results, a significant association was observed between the rs12979860 SNP and SC of HCV infection. The results indicated that the ORs of SC from hepatitis C virus infection were 2.75 times higher in those with cytokine gene polymorphisms (95% CI, 2.23 to 3.38). Moreover, it was found that the prevalence of rs12979860 CC was 0.33 with 95 CI 0.28-0.38 in genotype 1 and was 0.40 with 95 CI 0.34-0.47 in other genotypes. Our meta-analysis results suggest that IL28B rs12979860 CC is a strong predictor for SC of hepatitis C infection in PEG IFN-a/RBV-treated patients.


Mortality in COVID-19: Further Evidence for a Sex-Based Difference in the OpenSAFELY Study.
Although COVID-19 death rates are lower in women compared to men, it is not clear whether this difference in mortality is due to sex (biological) based factors, comorbidities that differ in men and women, or gender influences. New evidence supports a sex-based difference in COVID-19 mortality. Data from the OpenSAFELY cohort study in 17 million adult patients in England demonstrate that COVID-19-related deaths were associated with male sex (hazard ratio 1.59; 95% confidence interval 1.53-1.65) when fully adjusted for age, low income, smoking, pre-existing diseases, and ethnicity. Women have stronger innate and adaptive responses to infection. It is hypothesized that biological differences in the immune system may have a role in the sex-based difference in mortality from COVID-19. The results of OpenSAFELY demonstrate the importance of collection and analysis of sex-disaggregated data in research and public surveillance.


The medical review officer: a potential role for the medical examiner.
Drug use in the workplace is a problem, both in terms of public health and expense. Workplace drug testing programs serve as deterrents to drug use. Model programs, such as that of the Department of Transportation, use urine screening and are federally regulated or follow federal standards. An essential participant in this process is the medical review officer (MRO), a licensed physician who interprets the laboratory results generated from a workplace drug testing program. As a result of their training and experience with toxicology, collection of evidence, testimony, and recognition of the physical signs of drug abuse, medical examiners and forensic pathologists are well suited to serve as MROs. Recent regulations require the completion of training courses and MRO certification as prerequisites for participation in federal drug testing programs. Several courses are available to train physicians to participate as MROs.


Fabrication and Properties of Zn-3Mg-1Ti Alloy as a Potential Biodegradable Implant Material.
A Zn-3Mg-1Ti alloy was fabricated by ultrasonic treatment of Zn-Mg alloy melt using a Ti ultrasonic radiation rod. The microstructure, phase structure, mechanical properties, degradation property, and in vitro cytotoxicity were investigated systematically. The obtained Zn-3Mg-1Ti alloy is composed of the Zn, Mg2Zn11, and TiZn16. Owing to the grain refinement and second phase reinforcement, the mechanical properties of Zn-3Mg-1Ti alloy is improved. In addition, the Zn-3Mg-1Ti alloy exhibits minimal cytotoxicity compared to pure Zn and Zn-1Ti alloy. Electrochemical tests show that the Zn-3Mg-1Ti alloy has an appropriate degradation rate in Hank's solution.


Ovarian cancer stem cells: A target for oncological therapy.
According to numerous studies, failures in treatment of ovarian cancer, i.e., a relapse and metastases, result from a small population of cancer stem cells (CSCs). They may also be responsible for tumor initiation. Cancer stem cells are resistant to chemoand radiotherapy. Eradication of CSCs may involve the application of salinomycin, metformin and Clostridium perfringens; the effect of anti-angiogenic factors remains controversial. Salinomycin is an antibiotic isolated from Streptomyces albus bacteria. Its CSC-eradicating effect has been demonstrated both in ovarian cancer cell lines and in women with breast cancer. Clostridium perfringens enterotoxin (CPE) has been demonstrated to destroy CSCs in ovarian cancer both in vivo and in vitro. Metformin, apart from its hypoglycemic effect, reduces the CSC population and inhibits the proliferation of neoplastic cells and angiogenesis. Cancer stem cells with expression of VEGFR1+ have been described as affecting circulating cancer cells and influencing the formation of metastases. Both positive and negative effects of anti-angiogenic therapy on the CSC population have been documented.


Timing of retirement and mortality--a cohort study of Swedish construction workers.
Recent studies indicate that early retirement per se may have a negative effect on health to such an extent that it increases mortality risk. One type of early retirement often referred to in these studies is retirement with disability pension/benefit. Given the overall objective of disability benefit programmes--to help the disabled live socially and economically satisfactory lives, freed from exposure to employment health hazards and thus avoid further declines in health--the finding is challenging. This paper examined the relationship between timing of retirement and mortality using a cohort of Swedish construction workers. The mortality risk of disability pensioners--excluding those with diagnoses normally connected to increased mortality--was compared with the risk of those continuing to work. Although initial indications were in line with earlier results, it became obvious that the increased mortality risk of disability pensioners did not depend on early retirement per se but on poor health before early retirement not explicitly recognized in the diagnosis on which the disability pension rested. The results indicate that there are no general differences in mortality depending on timing of retirement. Future studies of mortality differences arising from working or not working must sufficiently control for health selection effects into the studied retirement paths.


Topical mydriatic and cycloplegic spray for Chinese children.
To assess the efficacy and tolerance of mydriatic and cycloplegic spray versus drops for Chinese children. The effects of the spray (cyclopentolate 0.25%, phenylephrine 0.625%, and tropicamide 0.5%) and the drops (cyclopentolate 1%, phenylephrine 0.5%, and tropicamide 0.5%) were evaluated in 29 children (58 eyes) in two separate sessions. There was a 1-week period between the applications of the spray and the drops. Dilated pupil size and refraction after cycloplegia were the primary outcome variables used to assess the efficacy. A subjective discomfort score was used to assess acceptance of the spray and the drops. The mean age of the study population was 4.33 +/- 1.39 years (range, 3 to 8 years). The mean pupil size was 6.9 mm for the spray and 6.6 mm for the drops. The spray appeared to be slightly more effective than the drops, with a mean difference of 0.3 mm that was statistically significant (P = .001, two-tailed t test). No statistically significant difference in cycloplegic response was found between the spray and the drops (P = .535, two-tailed t test). Administration of the spray caused less discomfort than did administration of the drops (P < .001, Wilcoxon signed-rank test). The spray system appears to be clinically equivalent to the drops for achieving effective pupil dilation and cycloplegia, even in a population with dark irides such as ours. Tolerability and acceptance improved because the spray was applied to the closed eyelids.


Antimicrobial resistance in nosocomial bloodstream infection associated with pneumonia and the value of systematic surveillance cultures in an adult intensive care unit.
To study the occurrence of multiple-drug-resistant pathogens in nosocomial bloodstream infection associated with pneumonia. To evaluate prediction of multiple drug resistance by systematic surveillance cultures. A retrospective study of a prospectively gathered cohort. Fifty-four-bed adult medical-surgical intensive care unit of a tertiary hospital. One hundred twelve intensive care unit patients with nosocomial bloodstream infection associated with pneumonia from 1992 through 2001. None. Concordance of blood cultures with prior surveillance culture was assessed. Surveillance cultures were taken routinely as thrice weekly urinary cultures and oral swabs, once weekly anal swabs, and thrice weekly tracheal aspirates in intubated patients. Tracheal surveillance cultures from 48 to 96 hrs before bloodstream infection and surveillance cultures from any site during the same intensive care unit episode but >or=48 hrs before bloodstream infection were evaluated separately. Forty-four bloodstream infections (39%) were caused by a multiple-drug-resistant pathogen. Multiple-drug-resistant pathogens were predicted by tracheal surveillance culture in 70% (concordant); in 15%, tracheal surveillance culture grew a multiple-drug-resistant pathogen not found in blood cultures (discordant). Multiple-drug-resistant pathogens were predicted by any surveillance culture in 88%, but these surveillance cultures grew additional multiple-drug-resistant pathogens not causing bloodstream infection in up to 46% of patients. In 86% of bloodstream infections, early (i.e., within 48 hrs) antibiotic therapy was appropriate. Patients were divided into four risk categories for multiple-drug-resistant bloodstream infection based on length of prior intensive care unit stay and prior antibiotic exposure. In patients with two risk factors, knowledge of surveillance cultures increased appropriateness of early antibiotic therapy from 75-79% to 90% (p<.05) while limiting use of broad-spectrum antibiotics such as antipseudomonal betalactams, fluoroquinolones, and carbapenems. In our intensive care unit, tracheal surveillance culture predicted multiple-drug-resistant etiology of bloodstream infection associated with pneumonia in 70% of patients but yielded discordant resistant pathogens in 15%. In the subgroup of patients with two risk factors for multiple-drug-resistant infection, incorporating results of surveillance cultures moderately contributed to adequacy of early antibiotic therapy while limiting antibiotic consumption.


Retrospective cohort study on risk factors for developing ischemic stroke.
There is a paucity of studies describing the risk factors for developing ischemic stroke in our region. The objective of the current study was to delineate the potential risk factors for the development of ischemic stroke. We have conducted a retrospective cohort hospitalbased study that has enrolled 231 subjects. The subjects have had presented to the emergency department in a tertiary hospital in the United Arab Emirates. Subjects were diagnosed with ischemic stroke within 24 hours of presentation. The main outcome measure was the development of ischemic stroke during an indexed hospital visit. The mean age was 47.5 ±3.2 with a higher preponderance of males over females (60.9%) and 48.1% were ≥ 65 years. The final logistic regression model for the development of ischemic stroke contains seven variables. In descending order, the seven predictive risk factors for the development of ischemic stroke were: hypertension (OR 6.1, CI 2.4-9.5; P = 0.029), coronary artery disease (OR 4.2, 3.7-9.1; P = 0.038), low physical activity (OR 4.2, CI 2.1-9.1; P = 0.035), history of previous stroke (OR 4.1, 1.4-3.4; P = 0.033), atrial fibrillation (OR 3.2, CI 2.6-8.2; P = 0.017), family history of stroke (OR 3.1, 1.3-6.9; P = 0.042) and diabetes mellitus (OR 2.7, CI 1.25-6.1; P = 0.035). The specificity of the model was 58.1%; the sensitivity was 86.1%, and the overall accuracy was 75.7%. It is prudent to control modifiable risk factors for the development of strokes such as hypertension, diabetes, atrial fibrillation, coronary artery disease, and low physical activity.


A comparative analysis of DNA methylation across human embryonic stem cell lines.
We performed a comparative analysis of the genome-wide DNA methylation profiles from three human embryonic stem cell (HESC) lines. It had previously been shown that HESC lines had significantly higher non-CG methylation than differentiated cells, and we therefore asked whether these sites were conserved across cell lines. We find that heavily methylated non-CG sites are strongly conserved, especially when found within the motif TACAG. They are enriched in splice sites and are more methylated than other non-CG sites in genes. We next studied the relationship between allele-specific expression and allele-specific methylation. By combining bisulfite sequencing and whole transcriptome shotgun sequencing (RNA-seq) data we identified 1,020 genes that show allele-specific expression, and 14% of CG sites genome-wide have allele-specific methylation. Finally, we asked whether the methylation state of transcription factor binding sites affects the binding of transcription factors. We identified variations in methylation levels at binding sites and found that for several transcription factors the correlation between the methylation at binding sites and gene expression is generally stronger than in the neighboring sequences. These results suggest a possible but as yet unknown functional role for the highly methylated conserved non-CG sites in the regulation of HESCs. We also identified a novel set of genes that are likely transcriptionally regulated by methylation in an allele-specific manner. The analysis of transcription factor binding sites suggests that the methylation state of cis-regulatory elements impacts the ability of factors to bind and regulate transcription.


Discovery of Cinnamylidene Derivative of Rhodanine with High Anthelmintic Activity against Rhabditis sp.
The treatment of parasitic infections requires the application of chemotherapy. In view of increasing resistance to currently in-use drugs, there is a constant need to search for new compounds with anthelmintic activity. A series of 16 cinnamylidene derivatives of rhodanine, including newly synthesized methoxy derivatives (1-11) and previously obtained chloro, nitro, and diethylamine derivatives (12-16), was investigated towards anthelmintic activity. Compounds (1-16) were evaluated against free-living nematodes of the genus Rhabditis sp. In the tested group of rhodanine derivatives, only compound 2 shows very high biological activity (LC50 = 0.93 µg/µL), which is higher than the reference drug albendazole (LC50 = 19.24 µg/µL). Crystal structures of two compounds, active 2 and inactive 4, were determined by the X-ray diffraction method to compare molecular geometry and search for differences responsible for observed biological activity/inactivity. Molecular modelling and selected physicochemical properties prediction were performed to assess the potential mechanism of action and applied in the search for an explanation as to why amongst all similar compounds only one is active. We can conclude that the tested compound 2 can be further investigated as a potential anthelmintic drug.


[The study of hemodynamic parameters of human internal carotid arteries depending on the age considering the sex and the localization of the artery].
The research of the ultrasound diameter, linear velocity and the resistance of internal carotid arteries of 647 people of both sexes aged from one to 74 years was conducted. Additionally, shear stress and the Reynolds number were calculated. During the period from early childhood to adolescence and from the first mature to old age there is an increase in the diameter of the internal carotid arteries. The phases of increased vascular resistance by the first period of childhood, adolescence and old age are observed. Volumetric flow rate has relatively stable parameters till adolescence, then it declines by old age. The average linear velocity, shear stress, and the Reynolds number diminish progressively twice with age. Laminar blood flow with local twists in the early stages of postnatal ontogenesis is characteristic of internal carotid arteries. The diameter of internal carotid arteries, vascular resistance index, blood flow velocity are higher in males than in females during most age periods. Shear stress in both internal carotid arteries during the age periods studied is symmetrical and has no sex differences.


External ultrasonic lipoplasty: an effective method of fat removal and skin shrinkage.
External ultrasonic lipoplasty is an effective method for the removal of localized fat and the fat due to moderate obesity. The ultrasound is externally applied and transmitted through the skin surface. The acoustic waves are selectively absorbed by previously injected tumescent fluid and fat. It is the combination of this acoustic wave and ultrasound-induced fluid streaming that facilitates fat removal. Multiple, 2.5- to 3.7-mm incisions are made, through which standard thin (2.3 to 3.5 mm) suction lipectomy cannulae are used to aspirate the emulsified fat and oil. A major advantage of this procedure is that superficial subdermal liposuction can be used safely, which enhances the thoroughness of fat removal and the contraction of the overlying skin. A total of 160 consecutive patients successfully underwent this procedure. Recovery was rapid, and patients returned to full activities within 24 to 48 hours. The skin remained soft, with minimal to no bruising throughout the entire postoperative period. The problems seen with internal ultrasonic liposuction, such as end hits and skin burns, were avoided. The large incisions required for internal ultrasound liposuction were not necessary. Previous models of externally applied ultrasound support current observations of the safety of external ultrasound lipoplasty. Only one small seroma was seen. External ultrasound lipoplasty is a safe, effective, and low-cost method of ultrasound-assisted removal of localized fat and the fat due to moderate obesity. Physician and patient satisfaction is high.


A dynamic model of membrane-bound phospholipase Cβ2 activation by Gβγ subunits.
Phospholipase C (PLC) β2, a well studied member of the family of enzymes that catalyze the hydrolysis of the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP₂) into secondary messengers, can be activated by the Gβγ subunits of heterotrimeric G-proteins in a manner that depends on the presence and composition of the associated phospholipid membrane surface. The N-terminal pleckstrin homology (PH) domain of PLCβ2 mediates both the response to Gβγ and membrane binding, but how these interactions are coupled to yield an activated catalytic core remains unknown. Here we propose a mechanism based on molecular models of truncated PLCβ2 in its activated form complexed with Gβγ and in the catalytically inactive/membrane-bound form, obtained with the application of protein-protein docking algorithms and coarse-grained molecular dynamics simulations. These models were probed experimentally, and the inferences were confirmed by results from a combination of molecular biology and fluorescence assays. Results from the dynamic simulations of the molecular models and their interactions with various lipid bilayers identify the determinants of PLCβ2-PH domain specificity for Gβγ and lipid membranes and suggest a mechanism for the previously reported dependence of Gβγ activation on the associated membrane composition. Together, these findings explain the roles of the different activators in terms of their effect on the orientations of the PH and catalytic core domains relative to the lipid membranes.


Healing and Antisecretory Effects of Aqueous Extract of Eremomastax speciosa (Acanthaceae) on Unhealed Gastric Ulcers.
This work investigated the healing and antisecretory effects of the aqueous extract of Eremomastax speciosa on "unhealed gastric ulcers" associated with gastric acid hypersecretion. "Unhealed gastric ulcers" were induced using indomethacin following the establishment of acetic-acid-induced chronic gastric ulcers. The extract (200 and 400 mg/kg, per os) was administered concomitantly with indomethacin (1 mg/kg, subcutaneously). The effects of the extract on both basal and histamine-stimulated gastric acid secretion were determined. Mucus secretion and oxidative stress parameters were measured, and histological assessment of ulcer healing was carried out. The extract significantly promoted the healing process in rats subjected to "unhealed gastric ulcers" (82.4-88.5% healing rates). Treatment with the extract significantly reduced the basal (25.95-49.51% reduction rates) and histamine-stimulated (24.25-47.41%) acid secretions. The healing effect of the extract was associated with a significant (p < 0.05) increase of mucus secretion and concentrations of antioxidant enzymes compared with the controls. The extract at the highest dose showed normalization of the mucosa, without glandular destruction and with the disappearance of fibrosis and lymphocyte infiltration. The abilities of the extract to increase mucus secretion, to reinforce antioxidant status, and to inhibit acid secretion would be some of the mechanisms by which this extract would accelerate the healing process in "unhealed gastric ulcers."


Increasing fitness is associated with fewer depressive symptoms during successful smoking abstinence among women.
Exercise has been hypothesized to curb increases in depressive symptoms often associated with smoking cessation. The relationship between increased fitness and changes in depressive symptoms was examined among 40 women who were abstinent at the end of an 8-week randomized controlled trial. Participants received group-based, cognitive-behavioral smoking cessation treatment plus either exercise or contact control. All participants completed maximal fitness tests and questionnaires, including the Centers for Epidemiological Studies Depression Scale at baseline and at post-treatment. Regardless of treatment assignment, women who increased fitness over the 8-week treatment period were more likely to have decreases in depressive symptoms. Results indicate that increased fitness may benefit women by attenuating the depressive symptoms often associated with nicotine withdrawal.


[Effects of rejuvenation by intense pulsed light and basic mechanism thereof].
To evaluate the effects of rejuvenation by intense pulsed light (IPL) and the mechanism thereof. Fifty-eight patients with photo aging were treated with IPL of single, double, or triple pulse pattern for 3 - 5 times with the intervals of 3 - 4 weeks. Three weeks after the last treatment, photography was conducted and the pictures underwent grading by the physicians and patients according to blind method. Skin specimens of the posteroinferior ear lobe or the nape were obtained from 4 patients to undergo HE staining, Uana orcein staining of elastin, immunohistochemical staining for collagenous fibers of types I and III, and transmission electron microscopy was conducted in 2 of the 4 patients. Skin digitalized image analysis was conducted on 34 female patients to measure and analyze the depth and width of dermatographs, roughness of skin. After the third treatment, the wrinkles and skin texture of 62.1% of the patients showed improvement, and 84.60% of the pigmented lesions and 81.25% of the vascular lesions showed improvement. Pathology showed that type I and type III collagen increased while elastin decreased, and the fibers were orderly re-arranged. Transmission electron microscopy showed that after treatment the fibroblasts increased in number and became more active in secretion and there were more collagen fibers orderly re-arranged in the stroma. Digitalized image analysis showed significant improvement in skin smoothness, depth, arithmetic average roughness and average roughness of skin texture (all P < 0.01). IPL is effective to improve the skin texture. The mechanism may be the increasing of the activity of the fibroblasts, and hyperplasia and re-arrangement of collagen and elastin.