Prediction of liability to orofacial clefting using genetic and craniofacial data from parents.
Cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) are separate clinical entities and for both polygenic multifactorial aetiology has been proposed. Parents of children with orofacial clefting have been shown to have distinctive differences in their facial shape when compared to matched controls. To test the hypothesis that genetic and morphometric factors predispose to orofacial clefting and that these markers differ for CL(P) and CP. Methods-Polymorphisms at the transforming growth factor alpha (TGFalpha) locus in 83 parents of children with nonsyndromic orofacial clefts were analysed, and their craniofacial morphology was assessed using lateral cephalometry. Parents of children with CL(P) and CP showed an increased frequency of the TGFalpha/TaqI C2 allele (RR=4.10, p=0.009) relative to the comparison group. Also the TGFalpha/BamHI A1 allele was more prevalent in the CP parents. MULTIVARIATE STATISTICAL ANALYSIS: Using stepwise logistic regression analysis the TGFalpha/TaqI C2 polymorphism provides the best model for liability to orofacial clefting. To determine the type of clefting a model involving interaction between the parental TGFalpha/BamHI and TGFalpha/RsaI genotypes showed the best fit. Using genotype only to predict the clefting defect in the children according to parental genotype, 68.3% could be correctly classified. By adding information on craniofacial measurements in the parents, 76% of CP and 94% of CL(P) parents could be correctly classified. This study provides a model for prediction of liability to orofacial clefting. These findings suggest that different molecular aberrations at the TGFalpha locus may modify the risk for CP and CL(P).


Chieh Mei Ching Yi: A randomized controlled trial of a culturally tailored HIV prevention intervention for Chinese massage parlor women in Los Angeles.
Asian heterosexual women in the U.S. have experienced relative rising HIV case rates, but there remain few studies and no evidence-based interventions that focus on this population. This study was a randomized controlled trial of a gender and ethnically tailored HIV prevention intervention for monolingual Chinese-speaking women who work as masseuses in Los Angeles. The intervention was two group-based sessions focused on HIV risk and prevention knowledge and condom skills. The control condition was a single-session HIV review. Participants were recruited using newspaper advertisements and referrals from agencies and massage schools. Two hundred women were randomly assigned to one of each condition. Retention in both conditions exceeded 90% at 3-month follow-up. Participants in both conditions demonstrated increases in knowledge on how to use male and female condoms. These effects were sustained at 3-month follow-up. The results highlight the possible efficacy of a one-workshop intervention in increasing HIV knowledge, but that more intensive participant interaction may be needed for improved condom use knowledge.


Automatic analysis of bronchus-artery dimensions to diagnose and monitor airways disease in cystic fibrosis.
Cystic fibrosis (CF) lung disease is characterised by progressive airway wall thickening and widening. We aimed to validate an artificial intelligence-based algorithm to assess dimensions of all visible bronchus-artery (BA) pairs on chest CT scans from patients with CF. The algorithm fully automatically segments the bronchial tree; identifies bronchial generations; matches bronchi with the adjacent arteries; measures for each BA-pair bronchial outer diameter (Bout), bronchial lumen diameter (Bin), bronchial wall thickness (Bwt) and adjacent artery diameter (A); and computes Bout/A, Bin/A and Bwt/A for each BA pair from the segmental bronchi to the last visible generation. Three datasets were used to validate the automatic BA analysis. First BA analysis was executed on 23 manually annotated CT scans (11 CF, 12 control subjects) to compare automatic with manual BA-analysis outcomes. Furthermore, the BA analysis was executed on two longitudinal datasets (Copenhagen 111 CTs, ataluren 347 CTs) to assess longitudinal BA changes and compare them with manual scoring results. The automatic and manual BA analysis showed no significant differences in quantifying bronchi. For the longitudinal datasets the automatic BA analysis detected 247 and 347 BA pairs/CT in the Copenhagen and ataluren dataset, respectively. A significant increase of 0.02 of Bout/A and Bin/A was detected for Copenhagen dataset over an interval of 2 years, and 0.03 of Bout/A and 0.02 of Bin/A for ataluren dataset over an interval of 48 weeks (all p<0.001). The progression of 0.01 of Bwt/A was detected only in the ataluren dataset (p<0.001). BA-analysis outcomes showed weak to strong correlations (correlation coefficient from 0.29 to 0.84) with manual scoring results for airway disease. The BA analysis can fully automatically analyse a large number of BA pairs on chest CTs to detect and monitor progression of bronchial wall thickening and bronchial widening in patients with CF.


Treatment patterns, outcomes and costs among elderly patients with chronic myeloid leukaemia: a population-based analysis.
Chronic myeloid leukaemia (CML) affects approximately 3000-5000 Americans each year, with the American Cancer Society expecting 4600 new cases in 2004. The incidence of CML increases with age; median age at diagnosis is 67 years. Long-term data on the economic burden associated with CML among the elderly are sparse. To fill this void, our study uses population-based data to evaluate longer-term treatment patterns, outcomes and costs among elderly Medicare beneficiaries following their diagnosis of CML. This retrospective cohort analysis used linked data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and Medicare claims. Study cohorts included 567 patients aged > or = 65 years newly diagnosed with CML between 1991 and 1993 in a SEER registry and followed for 5 years or until death, whichever occurred first. In addition, 567 control patients without CML matched 1 : 1 by age and sex (average age 78 years, 52% male) were included. The costs of care were based on total Medicare payments (in constant 1998 dollars). Groups were generally similar in terms of nonmatched variables. Five years following diagnosis, 13% of CML patients were still alive versus 68% of the control patients (median survival: 14 months vs > 60 months, respectively). The average total Medicare payments were USD35,785 for CML patients versus USD21,161 for control subjects (monthly payments: USD1688 vs USD428, respectively; p < 0.001). Approximately 25% of CML patients underwent Medicare-covered cancer treatment (11% outpatient chemotherapy, 6% inpatient chemotherapy and 8% outpatient interferon-alpha therapy). Younger patients and those diagnosed in the later years were most likely to be treated. Costs for treated patients were higher, and they lived longer. Our findings suggest low treatment rates, and substantial excess mortality and costs associated with CML among the elderly. The recent introduction of imatinib has dramatically changed the treatment of CML, which is likely to cause important changes to the economic burden of CML. Our results can be used as a baseline for evaluating the impact of such new therapies as data from clinical trials become available. Further work is needed to characterise this disease and the complex factors that influence treatment decisions and associated health outcomes in elderly patients.


Division delay induced in Escherichia coli by near-ultraviolet radiation.
Beams of near-ultraviolet radiation at several principal emission lines of a mercury arc were isolated with a grating monochromator and directed upon cell suspensions. During subsequent incubation at room temperature in Nutrient Broth, the population was studied by removing samples and obtaining cell numbers and cell size distributions with an electronic cell counter. Division delay without lethality was observed. The shapes of the dose-response curves for induction, the doses of near-ultraviolet radiation required, and the action spectrum for division delay were found to be similar to those for growth delay (in broth) and for photoprotection. These findings indicate that all three effects, division delay, growth delay, and photoprotection, are induced by a common type of critical event. Changes in cell size distribution in the culture during incubation in Nutrient Broth after near-ultraviolet irradiation are very similar for control and irradiated populations, although these changes occur at a much later time in the irradiated population. This indicates that, in Nutrient Broth, the population recovers completely from the inhibition of growth and division, thus justifying use of the term "delay," and suggesting that the damage is nongenetic.


An electron microscope study of the early postnatal development of the visual cortex of the hooded rat.
Synaptic plasticity in response to environmental events has been clearly demonstrated in the visual cortex of the rat, but no detailed data concerning the course of early synaptogenesis in this area are available. In this study, synaptogenesis in the visual cortex of hooded rats at 1, 3, 5, 7 and 10 postnatal days of age (P1-P10) was examined with electron microscopy. The cortex was divided into the molecular layer, the superficial layers (II-IV) and deep layers (V-VI). In the visual cortex at P1, very few synapses are present in the molecular and deep layers and virtually none in the yet undifferentiated layers II-IV that compose the cortical plate at this age. The synapses that are present are axodendritic and often symmetrical with little membrane thickening and few vesicles. Axosomatic synapses were seen as early as P3 but very rarely. There are marked increases in axodendritic synaptic density and maturity with increasing age. By P7 and P10, many synapses appear mature in form and the majority can be classified a symmetrical. Axospinal synapses first appeared at P7 and were more frequent by P10. However, this classification was somewhat uncertain since no spinal apparatus was detected. Rate of synaptogenesis appeared to increase over the ages studied and showed no signs of leveling off except in the deep layers. Synaptic length was extremely variable and did not change systematically with age.


Osteoid osteoma: the uniquely innervated bone tumor.
Osteoid osteomas are benign bone-forming tumors that despite their small size (<2.0 cm) characteristically produce severe nocturnal bone pain that is relieved by aspirin. This typical clinical presentation is virtually unique among bone tumors. Histologically, osteoid osteomas are circumscribed nodules of woven bone and osteoid with prominent osteoblastic rimming (the nidus), surrounded by thickened cortical and trabecular bone and loose fibrovascular tissue (the reactive zone). Prostaglandins mediate the pain of osteoid osteomas, but there have been few studies of their innervation. We investigated 34 osteoid osteomas using a streptavidin immunohistochemical technique and a panel of antibodies to neural and neural-associated antigens (phosphorylated neurofilament, neurofilament, and S-100 protein). Whenever possible, sections of the nidus and the reactive zone were stained. As controls, we stained other bone tumors that can be painful, including 10 osteoblastomas, 5 osteosarcomas, 6 giant cell tumors, 4 chondroblastomas, 3 aneurysmal bone cysts, and 6 cases of fibrous dysplasia. Twenty-five osteoid osteomas contained phosphorylated neurofilament-, neurofilament-, and/or S-100-positive nerve fibers in the reactive zone around the nidus and/or in the nidus. The nerve fibers were larger and more abundant in the reactive zone than in the nidus, and they were occasionally visible on hematoxylin- and eosin-stained slides on retrospective review. The smaller nerve fibers within the nidi were never identified, even after extensive review of those slides. In the nine cases in which nerve fibers were not identified, the sampled tissue consisted only of nidus. None of the control "bone tumors" contained detectable nerve fibers within their substance or in the adjacent peripheral bone. The nerve supply of osteoid osteoma seems unique among bone tumors, and it might serve as a marker in diagnostically difficult cases.


Live-cell tracking using SIFT features in DIC microscopic videos.
In this paper, a novel motion-tracking scheme using scale-invariant features is proposed for automatic cell motility analysis in gray-scale microscopic videos, particularly for the live-cell tracking in low-contrast differential interference contrast (DIC) microscopy. In the proposed approach, scale-invariant feature transform (SIFT) points around live cells in the microscopic image are detected, and a structure locality preservation (SLP) scheme using Laplacian Eigenmap is proposed to track the SIFT feature points along successive frames of low-contrast DIC videos. Experiments on low-contrast DIC microscopic videos of various live-cell lines shows that in comparison with principal component analysis (PCA) based SIFT tracking, the proposed Laplacian-SIFT can significantly reduce the error rate of SIFT feature tracking. With this enhancement, further experimental results demonstrate that the proposed scheme is a robust and accurate approach to tackling the challenge of live-cell tracking in DIC microscopy.


3D printing of PLGA scaffolds for tissue engineering.
We proposed a novel method of generation of bioresorbable polymeric scaffolds with specified architectonics for tissue engineering using extrusion three-dimensional (3D) printing with solutions of polylactoglycolide in tetraglycol with their subsequent solidifying in aqueous medium. On the basis of 3D computer models, we obtained the matrix structures with interconnected system of pores ranging in size from 0.5 to 500 µm. The results of in vitro studies using cultures of line NIH 3Т3 mouse fibroblasts, floating islet cultures of newborn rabbit pancreas, and mesenchymal stem cells of human adipose tissue demonstrated the absence of cytotoxicity and good adhesive properties of scaffolds in regard to the cell cultures chosen. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 104-109, 2017.


A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma.
This multicenter, first-in-human study evaluated the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of the anti-CS1 monoclonal antibody elotuzumab. A standard 3 + 3 design was used to determine maximum tolerated dose; dose-limiting toxicities were assessed during cycle 1. Thirty-five patients with relapsed/refractory multiple myeloma were treated with intravenous elotuzumab at doses ranging from 0.5 to 20 mg/kg every 2 weeks. Patients who achieved at least stable disease after 4 treatments could receive another 4 treatments. No maximum tolerated dose was identified up to the maximum planned dose of 20 mg/kg. The most common adverse events, regardless of attribution, were cough, headache, back pain, fever, and chills. Adverse events were generally mild to moderate in severity, and adverse events attributed to study medication were primarily infusion-related. Plasma elotuzumab levels and terminal half-life increased with dose whereas clearance decreased, suggesting target-mediated clearance. CS1 on bone marrow-derived plasma cells was reliably saturated (≥ 95%) at the 10-mg/kg and 20-mg/kg dose levels. Using the European Group for Bone and Marrow Transplantation myeloma response criteria, 9 patients (26.5%) had stable disease. In summary, elotuzumab was generally well tolerated in this population, justifying further exploration of this agent in combination regimens.


Deciphering the enigma between low bioavailability and high anti-hepatic fibrosis efficacy of Yinchen Wuling powder based on drug metabolism and network pharmacology.
Yinchen Wuling powder (YCWLP) is a famous traditional Chinese medicine formula with the effect of "removing jaundice and eliminating dampness", which has the potential to prevent and treat hepatic fibrosis (HF). However, the mechanism of the active ingredients of YCWLP in treating HF remains to be clarified. This study aims to investigate the in vivo metabolic profile of YCWLP and the mechanism of its gut microbiota-mediated therapeutic effect on HF via network pharmacology. In this comprehensive study, the UHPLC-FT-ICR-MS platform was used for the systematic characterization of the in vivo metabolic profile of YCWLP, and the mediating effect of gut microbiota was elucidated by comparing the differences of metabolites between the normal rats and pseudo germ-free rats administrated with YCWLP. Then, the identified active ingredients of YCWLP metabolized by gut microbiota and their targets associated with HF were used for further network pharmacological analysis, including the construction of PPI network, GO and KEGG enrichment and compound-target-pathway-disease network. Overall, 41 prototype compounds and 138 metabolites were identified in the biosamples after YCWLP administration. Among them, 15 drug prototypes are clearly metabolized by gut microbiota, and 91 metabolites showed significant differences between the N-YCWLP group and the PGF-YCWLP group, which might be attributed to the mediation of gut microbiota. Network pharmacology studies on the aforementioned 15 prototype components indicated crucial roles of arginine biosynthesis and complement and coagulation cascades-related genes such as PLG, NOS3, GC and F2 in the treatment of HF by YCWLP mediated by gut microbiota. The therapeutic effects of multiple active ingredients in YCWLP on HF depend on the metabolism of gut microbiota. This study offers novel insights into the relationship between bioactive chemical constituents and the action mechanism of YCWLP against HF.


The fungal pathogen Candida albicans autoinduces hyphal morphogenesis by raising extracellular pH.
pH homeostasis is critical for all organisms; in the fungal pathogen Candida albicans, pH adaptation is critical for virulence in distinct host niches. We demonstrate that beyond adaptation, C. albicans actively neutralizes the environment from either acidic or alkaline pHs. Under acidic conditions, this species can raise the pH from 4 to >7 in less than 12 h, resulting in autoinduction of the yeast-hyphal transition, a critical virulence trait. Extracellular alkalinization has been reported to occur in several fungal species, but under the specific conditions that we describe, the phenomenon is more rapid than previously observed. Alkalinization is linked to carbon deprivation, as it occurs in glucose-poor media and requires exogenous amino acids. These conditions are similar to those predicted to exist inside phagocytic cells, and we find a strong correlation between the use of amino acids as a cellular carbon source and the degree of alkalinization. Genetic and genomic approaches indicate an emphasis on amino acid uptake and catabolism in alkalinizing cells. Mutations in four genes, STP2, a transcription factor regulating amino acid permeases, ACH1 (acetyl-coenzyme A [acetyl-CoA] hydrolase), DUR1,2 (urea amidolyase), and ATO5, a putative ammonia transporter, abolish or delay neutralization. The pH changes are the result of the extrusion of ammonia, as observed in other fungi. We propose that nutrient-deprived C. albicans cells catabolize amino acids as a carbon source, excreting the amino nitrogen as ammonia to raise environmental pH and stimulate morphogenesis, thus directly contributing to pathogenesis. Candida albicans is the most important fungal pathogen of humans, causing disease at multiple body sites. The ability to switch between multiple morphologies, including a rounded yeast cell and an elongated hyphal cell, is a key virulence trait in this species, as this reversible switch is thought to promote dissemination and tissue invasion in the host. We report here that C. albicans can actively alter the pH of its environment and induce its switch to the hyphal form. The change in pH is caused by the release of ammonia from the cells produced during the breakdown of amino acids. This phenomenon is unprecedented in a human pathogen and may substantially impact host physiology by linking morphogenesis, pH adaptation, carbon metabolism, and interactions with host cells, all of which are critical for the ability of C. albicans to cause disease.


Do we need to be concerned about dental caries in the coming millennium?
Dental caries continues to be a pubic health problem despite claims that 50% of schoolchildren are caries-free. There are widespread variations in the prevalence of caries worldwide. Caries lesions are the clinical manifestation of a pathogenic process that may have been occurring on the tooth surface for months or years. Acid production by bacteria embedded in a biofilm termed "dental plaque" is a key aspect of the pathogenesis of dental caries; nevertheless, the ability of micro-organisms to survive in a hostile acid milieu and the influence of fluoride and additional agents on this acid tolerance receive scant attention. Study of cariogenic micro-organisms largely has been limited to observations made on them in the planktonic state; clearly dental caries is essentially a surface phenomenon, and micro-organisms behave distinctively when grown on a surface. Although significant progress has been made in our understanding of the etiology, pathogenesis, and prevention of dental caries, it still remains a scientific and clinical enigma worthy of the attention of the best scientists.


Single Atom Stabilization of Phosphinate Ester-Containing Rhodamines Yields Cell Permeable Probes for Turn-On Photoacoustic Imaging.
Photoacoustic imaging (PAI) is an emerging imaging technique that uses pulsed laser excitation with near-infrared (NIR) light to elicit local temperature increases through non-radiative relaxation events, ultimately leading to the production of ultrasound waves. The classical xanthene dye scaffold has found numerous applications in fluorescence imaging, however, xanthenes are rarely utilized for PAI since they do not typically display NIR absorbance. Herein, we report the ability of Nebraska Red (NR) xanthene dyes to produce photoacoustic (PA) signal and provide a rational design approach to reduce the hydrolysis rate of ester containing dyes, affording cell permeable probes. To demonstrate the utility of this approach, we construct the first cell permeable rhodamine-based, turn-on PAI imaging probe for hypochlorous acid (HOCl) with maximal absorbance within the range of commercial PA instrumentation. This probe, termed SNR700 -HOCl, is capable of detecting exogenous HOCl in mice. This work provides a new set of rhodamine-based PAI agents as well as a rational design approach to stabilize esterified versions of NR dyes with desirable properties for PAI. In the long term, the reagents described herein could be utilized to enable non-invasive imaging of HOCl in disease-relevant model systems.


The Feasibility of a Completely Automated Total IV Anesthesia Drug Delivery System for Cardiac Surgery.
In this pilot study, we tested a novel automatic anesthesia system for closed-loop administration of IV anesthesia drugs for cardiac surgical procedures with cardiopulmonary bypass. This anesthesia drug delivery robot integrates all 3 components of general anesthesia: hypnosis, analgesia, and muscle relaxation. Twenty patients scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Propofol, remifentanil, and rocuronium were administered using closed-loop feedback control. The main objective was the feasibility of closed-loop anesthesia defined as successful automated cardiac anesthesia without manual override by the attending anesthesiologist. Secondary qualitative observations were clinical and controller performances. The clinical performance of hypnosis control was the efficacy to maintain a bispectral index (BIS) of 45. To evaluate the hypnosis performance, BIS values were stratified into 4 categories: "excellent," "good," "poor," and "inadequate" hypnosis control defined as BIS values within 10%, ranging from 11% to 20%, ranging from 21% to 30%, or >30% of the target value, respectively. The clinical performance of analgesia was the efficacy to maintain NociMap values close to 0. The analgesia performance was assessed classifying the NociMap values in 3 pain control groups: -33 to +33 representing excellent pain control, -34 to -66 and +34 to +66 representing good pain control, and -67 to -100 and +67 to +100 representing insufficient pain control. The controller performance was calculated using the Varvel parameters. Robotic anesthesia was successful in 16 patients, which is equivalent to 80% (97.5% confidence interval [CI], 53%-95%) of the patients undergoing cardiac surgery. Four patients were excluded from the final analysis because of technical problems with the automated anesthesia delivery system. The secondary qualitative observations revealed that the clinical performance of hypnosis allowed an excellent and good control during 70% (97.5% CI, 63%-76%) of maintenance time and an insufficient clinical performance of analgesia for only 3% (97.5% CI, 1%-6%) of maintenance time. The completely automated closed-loop system tested in this investigation could be used successfully and safely for cardiac surgery necessitating cardiopulmonary bypass. The results of the present trial showed satisfactory clinical performance of anesthesia control.


Genomic copy number variations in three Southeast Asian populations.
Research on the role of copy number variations (CNVs) in the genetic risk of diseases in Asian populations has been hampered by a relative lack of reference CNV maps for Asian populations outside the East Asians. In this article, we report the population characteristics of CNVs in Chinese, Malay, and Asian Indian populations in Singapore. Using the Illumina Human 1M Beadchip array, we identify 1,174 CNV loci in these populations that corroborated with findings when the same samples were typed on the Affymetrix 6.0 platform. We identify 441 novel loci not previously reported in the Database of Genomic Variations (DGV). We observe a considerable number of loci that span all three populations and were previously unreported, as well as population-specific loci that are quite common in the respective populations. From this we observe the distribution of CNVs in the Asian Indian population to be considerably different from the Chinese and Malay populations. About half of the deletion loci and three-quarters of duplication loci overlap UCSC genes. Tens of loci show population differentiation and overlap with genes previously known to be associated with genetic risk of diseases. One of these loci is the CYP2A6 deletion, previously linked to reduced susceptibility to lung cancer.


Recessive mutation identifies auxin-repressed protein ARP1, which regulates growth and disease resistance in tobacco.
To study the molecular mechanism that underpins crosstalk between plant growth and disease resistance, we performed a mutant screening on tobacco and created a recessive mutation that caused the phenotype of growth enhancement and resistance impairment (geri1). In the geri1 mutant, growth enhancement accompanies promoted expression of growth-promoting genes, whereas repressed expression of defense response genes is consistent with impaired resistance to diseases caused by viral, bacterial, and oomycete pathogens. The geri1 allele identifies a single genetic locus hypothetically containing the tagged GERI1 gene. The isolated GERI1 gene was predicted to encode auxin-repressed protein ARP1, which was determined to be 13.5 kDa in size. The ARP1/GERI1 gene was further characterized as a repressor of plant growth and an activator of disease resistance based on genetic complementation, gene silencing, and overexpression analyses. ARP1/GERI1 resembles pathogen-associated molecular patterns and is required for them to repress plant growth and activate plant immunity responses. ARP1/GERI1 represses growth by inhibiting the expression of AUXIN RESPONSE FACTOR gene ARF8, and ARP1/GERI1 recruits the NPR1 gene, which is essential for the salicylic-acid-mediated defense, to coregulate disease resistance. In conclusion, ARP1/GERI1 is an integral regulator for crosstalk between growth and disease resistance in the plant.


[Prenatal diagnosis in dermatology: contribution of the ultrastructural study].
Fetoscopy and fetal skin biopsy have together played an important role for antenatal diagnosis of various hereditary skin disorders (genodermatoses). The fetus and placenta can be visualized directly and skin biopsy samples can be obtained for light and electron microscopic studies, tissue culture and biochemical analysis. These techniques have been used successfully in the prenatal diagnosis or exclusion of some types of epidermolysis bullosa, ichthyosis, Chediak-Higashi syndrome, oculocutaneous albinism and anhydrotic ectodermal dysplasia in fetuses known to be at risk from these diseases. The purpose of this report is to describe the current methods of fetoscopy and fetal skin biopsy and to review their main dermatological indications. Complications associated with these procedures are also discussed.


Impact of parental migration on oral health outcomes of left-behind school-aged children in Luchuan, southern China.
With rapid urbanization in China, an increasing number of rural adults have migrated to cities to seek job opportunities, leaving their school-aged children behind. These left-behind children (LBC) without one or both parents usually receive less attention from their caregivers. Whether the parental migration affects the children's oral health is not well understood. This study aimed to explore the differences in dental caries status and oral health-related behaviors between children with different parental migration experiences in a rural area of Southern China. A cross-sectional study was conducted in Luchuan County of Guangxi Province in 2015. A total of 1085 school children aged 8-12 participated in this study. Participants' demographic characteristics, parental migration information, and eating and oral hygiene habits were collected using a self-administered questionnaire. Dental caries of permanent teeth was examined using the decayed, missing, and filled tooth (DMFT) index recommended by the World Health Organization. Dental caries experience and oral health-related behaviors were compared between LBC and non-LBC, as well as children with different experiences of parental migrations. The impact of various parental migration attributes on LBC oral health outcomes was examined by univariate and multivariate analyses. Among the school-aged children examined, 60.9% of them were LBC. Only 29.7% of the children brushed their teeth regularly; 86.5% of them did not know what fluoride toothpaste was. Caries prevalence was 51.4% for LBC and 40.8% for non-LBC (p < 0.001). The LBC experienced a greater DMFT mean (1.20 ± 1.59) compared to the non-LBC (0.85 ± 1.30) (p < 0.001). Oral health-related behaviors were not significantly different between LBC and non-LBC. Dental caries experience and oral health-related behaviors were not related to the type or duration of parental migration. Multiple regression analyses showed that parental migration was one of significant predictors of children's caries outcome; LBC had a higher risk to caries than non-LBC (95% CI =1.26, 2.09). These findings indicate that parental migration could be a significant risk factor for caries development among 8- to 12-year-old school children in rural China.


Coordination between the polymerase and RNase H activity of HIV-1 reverse transcriptase.
Replication of human immunodeficiency virus 1 (HIV-1) involves conversion of its single-stranded RNA genome to double-stranded DNA, which is integrated into the genome of the host. This conversion is catalyzed by reverse transcriptase (RT), which possesses DNA polymerase and RNase H domains. The available crystal structures suggest that at any given time the RNA/DNA substrate interacts with only one active site of the two domains of HIV-1 RT. Unknown is whether a simultaneous interaction of the substrate with polymerase and RNase H active sites is possible. Therefore, the mechanism of the coordination of the two activities is not fully understood. We performed molecular dynamics simulations to obtain a conformation of the complex in which the unwound RNA/DNA substrate simultaneously interacts with the polymerase and RNase H active sites. When the RNA/DNA hybrid was immobilized at the polymerase active site, RNase H cleavage occurred, experimentally verifying that the substrate can simultaneously interact with both active sites. These findings demonstrate the existence of a transient conformation of the HIV-1 RT substrate complex, which is important for modulating and coordinating the enzymatic activities of HIV-1 RT.


Repeated cocaine administration induces gene expression changes through the dopamine D1 receptors.
Drug addiction involves compulsive drug-seeking and drug-taking despite known adverse consequences. The enduring nature of drug addiction suggests that repeated exposure to abused drugs leads to stable alterations that likely involve changes in gene expression in the brain. The dopamine D1 receptor has been shown to mediate the long-term behavioral effects of cocaine. To examine how the persistent behavioral effects of cocaine correlate with underlying changes in gene expression, we have used D1 receptor mutant and wild-type mice to identify chronic cocaine-induced gene expression changes mediated via the D1 receptors. We focused on the caudoputamen and nucleus accumbens, two key brain regions that mediate the long-term effects of cocaine. Our analyses demonstrate that repeated cocaine administration induces changes in the expression of 109 genes, including those encoding the stromal cell-derived factor I, insulin-like growth factor binding protein 6, sigma 1 receptor, regulators of G-protein signaling protein 4, Wnt1 responsive Cdc42 homolog, Ca2+/calmodulin-dependent protein kinase II alpha subunit, and cyclin D2, via the D1 receptors. Moreover, the seven genes contain AP-1 binding sites in their promoter regions. These results suggest that genes encoding certain extracellular factors, membrane receptors and modulators, and intracellular signaling molecules, among others, are regulated by cocaine via the D1 receptor, and these AP-1 transcription complex-regulated genes might contribute to persistent cocaine-induced behavioral changes.


Role of source matrix in the bioavailability of polycyclic aromatic hydrocarbons to deposit-feeding benthic invertebrates.
The bioavailability of polycyclic aromatic hydrocarbons (PAHs) to benthic organisms is complicated by the variety of ways that they are introduced to coastal waters (dissolved, as nonaqueous phase liquids, and tightly bound to soot, coal, tire rubber, and eroded shale). In order to better understand the controlling variables that affect chemical and biological availability of PAHs, a study was conducted in which three deposit-feeding infaunal benthic invertebrate species (Cirriformia grandis, Clymenella torquata, and Macoma balthica) were exposed to sediments amended with PAH-rich materials (coal dust, tire rubber, diesel soot, creosote, crude oil, and fuel oil). Lipid and organic carbon normalized bioaccumulation factors (BAF(1oc)s) were calculated after 20 d of exposure and PAH bioavailability from the different treatments was assessed. Bioaccumulation of coal-derived PAHs usually was too low to be measured, though PAHs associated with soot and tire rubber showed significant accumulation in organism tissues. Polycyclic aromatic hydrocarbons from the fuel oil, creosote, and crude oil treatments were more bioavailable than PAHs bound in solid carbonaceous matrices (soot, coal, and tire rubber). Desorption of PAHs from the amended sediments into seawater also was measured using XAD resin. As was observed with bioaccumulation, PAHs in coal were desorbed the least; tire rubber and diesel soot were intermediate; and creosote, fuel oil, and crude oil desorbed to the greatest extent. In only one out of the three species evaluated was PAH bioaccumulation related to extent of desorption after 20 d. Decoupling between biological and chemical availability may be due to species-specific factors such as surfactant-mediated solubilization in the guts of some deposit-feeding organisms. A significant finding of this work was the demonstration that PAHs associated with soot and tire rubber in their native state (rather than experimentally added) are available to some benthic biota.


Mating type switching in the tetrapolar basidiomycete Agrocybe aegerita.
The study of fruiting in the basidiomycete Agrocybe aegerita has shown that some haploid homokaryotic strains can spontaneously switch their mating specificities at the two unlinked A and B mating type factors. This event causes the dikaryotisation of primary homokaryons without plasmogamy and leads to the differentiation of sporulating fruit-bodies (pseudo-homokaryotic fruiting). For each mating type factor, the genetic analyses have revealed that: (1) parental and switched mating types segregate meiotically as Mendelian markers, (2) a total of six switched mating type factors (two parental and four nonparental) were obtained from a wild strain, (3) most of the nonparental factors have specificities differing from those of a large series of wild factors, (4) strains with the same expressed mating type can generate different specificities, (5) switching is always restricted to the same mating type in a homokaryon, (6) nonparental types can switch again, and (7) meiosis fixes the specificities to which switching can occur. This suggests, for the first time in filamentous fungi, the existence of a mechanism analogous to the mating type switching in yeasts. We hypothese that both A and B mating type regions in A. aegerita are constituted of three loci, one specialized in expression and two other carrying silent information. Mating type switching in homokaryotic strains would occur by copy transposition of silent A and B information into the expression loci. Moreover, we propose that during meiosis the silent loci are substituted by copies of the expressed loci.


Virus-induced diseases of the eye: the role of herpesviruses in retinitis.
The herpesviruses are now recognized as major causes of acute retinitis, principally in the immunocompromised host, but also in otherwise healthy people. Clinical and laboratory features can help determine which herpesvirus is likely to be involved, and disease due to certain types can be treated successfully. Herpes ocular infection is a field of active laboratory research.


PAPD5-mediated 3' adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease.
Next-generation sequencing experiments have shown that microRNAs (miRNAs) are expressed in many different isoforms (isomiRs), whose biological relevance is often unclear. We found that mature miR-21, the most widely researched miRNA because of its importance in human disease, is produced in two prevalent isomiR forms that differ by 1 nt at their 3' end, and moreover that the 3' end of miR-21 is posttranscriptionally adenylated by the noncanonical poly(A) polymerase PAPD5. PAPD5 knockdown caused an increase in the miR-21 expression level, suggesting that PAPD5-mediated adenylation of miR-21 leads to its degradation. Exoribonuclease knockdown experiments followed by small-RNA sequencing suggested that PARN degrades miR-21 in the 3'-to-5' direction. In accordance with this model, microarray expression profiling demonstrated that PAPD5 knockdown results in a down-regulation of miR-21 target mRNAs. We found that disruption of the miR-21 adenylation and degradation pathway is a general feature in tumors across a wide range of tissues, as evidenced by data from The Cancer Genome Atlas, as well as in the noncancerous proliferative disease psoriasis. We conclude that PAPD5 and PARN mediate degradation of oncogenic miRNA miR-21 through a tailing and trimming process, and that this pathway is disrupted in cancer and other proliferative diseases.


Photoanodes with Fully Controllable Texture: The Enhanced Water Splitting Efficiency of Thin Hematite Films Exhibiting Solely (110) Crystal Orientation.
Hematite, α-Fe2O3, is considered as one of the most promising materials for sustainable hydrogen production via photoelectrochemical water splitting with a theoretical solar-to-hydrogen efficiency of 17%. However, the poor electrical conductivity of hematite is a substantial limitation reducing its efficiency in real experimental conditions. Despite of computing models suggesting that the electrical conductivity is extremely anisotropic, revealing up to 4 orders of magnitude higher electron transport with conduction along the (110) hematite crystal plane, synthetic approaches allowing the sole growth in that direction have not been reported yet. Here, we present a strategy for controlling the crystal orientation of very thin hematite films by adjusting energy of ion flux during advanced pulsed reactive magnetron sputtering technique. The texture and effect of the deposition mode on the film properties were monitored by XRD, conversion electron Mössbauer spectroscopy, XPS, SEM, AFM, PEC water splitting, IPCE, transient photocurrent measurements, and Mott-Schottky analysis. The precise control of the synthetic conditions allowed to fabricate hematite photoanodes exhibiting fully textured structures along (110) and (104) crystal planes with huge differences in photocurrents of 0.65 and 0.02 mA cm(-2) (both at 1.55 V versus RHE), respectively. The photocurrent registered for fully textured (110) film is among record values reported for thin planar films. Moreover, the developed fine-tuning of crystal orientation having a huge impact on the photoefficiency would induce further improvement of thin hematite films mainly if cation doping will be combined with the controllable texture.


Production of complex multiantennary N-glycans in Nicotiana benthamiana plants.
In recent years, plants have been developed as an alternative expression system to mammalian hosts for the production of therapeutic proteins. Many modifications to the plant glycosylation machinery have been made to render it more human because of the importance of glycosylation for functionality, serum half-life, and the safety profile of the expressed proteins. These modifications include removal of plant-specific β1,2-xylose and core α1,3-fucose, and addition of bisecting N-acetylglucosamine, β1,4-galactoses, and sialic acid residues. Another glycosylation step that is essential for the production of complex human-type glycans is the synthesis of multiantennary structures, which are frequently found on human N-glycans but are not generated by wild-type plants. Here, we report both the magnICON-based transient as well as stable introduction of the α1,3-mannosyl-β1,4-N-acetylglucosaminyltransferase (GnT-IV isozymes a and b) and α1,6-mannosyl-β1,6-N-acetylglucosaminyltransferase (GnT-V) in Nicotiana benthamiana plants. The enzymes were targeted to the Golgi apparatus by fusing their catalytic domains to the plant-specific localization signals of xylosyltransferase and fucosyltransferase. The GnT-IV and -V modifications were tested in the wild-type background, but were also combined with the RNA interference-mediated knockdown of β1,2-xylosyltransferase and α1,3-fucosyltransferase. Results showed that triantennary Gn[GnGn] and [GnGn]Gn N-glycans could be produced according to the expected activities of the respective enzymes. Combination of the two enzymes by crossing stably transformed GnT-IV and GnT-V plants showed that up to 10% tetraantennary [GnGn][GnGn], 25% triantennary, and 35% biantennary N-glycans were synthesized. All transgenic plants were viable and showed no aberrant phenotype under standard growth conditions.


Comparison of Carbon Isotope Ratio Measurement of the Vanillin Methoxy Group by GC-IRMS and 13C-qNMR.
Site-specific carbon isotope ratio measurements by quantitative 13C NMR (13C-qNMR), Orbitrap-MS, and GC-IRMS offer a new dimension to conventional bulk carbon isotope ratio measurements used in food provenance, forensics, and a number of other applications. While the site-specific measurements of carbon isotope ratios in vanillin by 13C-qNMR or Orbitrap-MS are powerful new tools in food analysis, there are a limited number of studies regarding the validity of these measurement results. Here we present carbon site-specific measurements of vanillin by GC-IRMS and 13C-qNMR for methoxy carbon. Carbon isotope delta (δ13C) values obtained by these different measurement approaches demonstrate remarkable agreement; in five vanillin samples whose bulk δ13C values ranged from -31‰ to -26‰, their δ13C values of the methoxy carbon ranged from -62.4‰ to -30.6‰, yet the difference between the results of the two analytical approaches was within ±0.6‰. While the GC-IRMS approach afforded up to 9-fold lower uncertainties and required 100-fold less sample compared to the 13C-qNMR, the 13C-qNMR is able to assign δ13C values to all carbon atoms in the molecule, not just the cleavable methoxy group.


The problem of valve prosthesis-patient mismatch.
Valve prostheses have played an important part in the past two decades in the management of patients with valvular heart disease. However, many of the devices used in valve replacement have introduced new clinical problems. This paper deals with some of the problems associated with valve replacement, including one not previously emphasized--valve prosthesis-patient mismatch, which may cause obstruction to ventricular outflow and/or inflow.


How Openness Enriches the Environment: Read More.
The recently proposed OFCI model and specifically the Environmental Enrichment Hypothesis state that Openness positively influences the development of cognitive abilities (Ziegler et al., 2012). It is assumed that Openness leads to engagement in more learning activities through creating an enriched environment (e.g., reading). However, despite positive evaluations of the OFCI model in general, there is little empirical research on this specific hypothesis. The current paper used a longitudinal design to test the positive impact of Openness on the frequency of reading activities in general and in the specific case of periods of unemployment. PIAAC (Programme for the International Assessment of Adult Competencies) data were used to fit structural equation models. The results show that Openness fosters greater engagement in reading activities over 3 years; a buffering function in case of unemployment could not be found. Theoretical and practical implications are discussed.


Nucleosome eviction and multiple co-factor binding predict estrogen-receptor-alpha-associated long-range interactions.
Many enhancers regulate their target genes via long-distance interactions. High-throughput experiments like ChIA-PET have been developed to map such largely cell-type-specific interactions between cis-regulatory elements genome-widely. In this study, we integrated multiple types of data in order to reveal the general hidden patterns embedded in the ChIA-PET data. We found characteristic distance features related to promoter-promoter, enhancer-enhancer and insulator-insulator interactions. Although a protein may have many binding sites along the genome, our hypothesis is that those sites that share certain open chromatin structure can accommodate relatively larger protein complex consisting of specific regulatory and 'bridging' factors, and may be more likely to form robust long-range deoxyribonucleic acid (DNA) loops. This hypothesis was validated in the estrogen receptor alpha (ERα) ChIA-PET data. An efficient classifier was built to predict ERα-associated long-range interactions solely from the related ChIP-seq data, hence linking distal ERα-dependent enhancers to their target genes. We further applied the classifier to generate additional novel interactions, which were undetected in the original ChIA-PET paper but were validated by other independent experiments. Our work provides a new insight into the long-range chromatin interactions through deeper and integrative ChIA-PET data analysis and demonstrates DNA looping predictability from ordinary ChIP-seq data.


Dropwort-induced metabolic reprogramming restrains YAP/TAZ/TEAD oncogenic axis in mesothelioma.
Over the past decade, newly designed cancer therapies have not significantly improved the survival of patients diagnosed with Malignant Pleural Mesothelioma (MPM). Among a limited number of genes that are frequently mutated in MPM several of them encode proteins that belong to the HIPPO tumor suppressor pathway. The anticancer effects of the top flower standardized extract of Filipendula vulgaris (Dropwort) were characterized in "in vitro" and "in vivo" models of MPM. At the molecular level, two "omic" approaches were used to investigate Dropwort anticancer mechanism of action: a metabolomic profiling and a phosphoarray analysis. We found that Dropwort significantly reduced cell proliferation, viability, migration and in vivo tumor growth of MPM cell lines. Notably, Dropwort affected viability of tumor-initiating MPM cells and synergized with Cisplatin and Pemetrexed in vitro. Metabolomic profiling revealed that Dropwort treatment affected both glycolysis/tricarboxylic acid cycle as for the decreased consumption of glucose, pyruvate, succinate and acetate, and the lipid metabolism. We also document that Dropwort exerted its anticancer effects, at least partially, promoting YAP and TAZ protein ubiquitination. Our findings reveal that Dropwort is a promising source of natural compound(s) for targeting the HIPPO pathway with chemo-preventive and anticancer implications for MPM management.


Isolation and characterization of avian influenza viruses, including highly pathogenic H5N1, from poultry in live bird markets in Hanoi, Vietnam, in 2001.
Since 1997, outbreaks of highly pathogenic (HP) H5N1 and circulation of H9N2 viruses among domestic poultry in Asia have posed a threat to public health. To better understand the extent of transmission of avian influenza viruses (AIV) to humans in Asia, we conducted a cross-sectional virologic study in live bird markets (LBM) in Hanoi, Vietnam, in October 2001. Specimens from 189 birds and 18 environmental samples were collected at 10 LBM. Four influenza A viruses of the H4N6 (n = 1), H5N2 (n = 1), and H9N3 (n = 2) subtypes were isolated from healthy ducks for an isolation frequency of over 30% from this species. Two H5N1 viruses were isolated from healthy geese. The hemagglutinin (HA) genes of these H5N1 viruses possessed multiple basic amino acid motifs at the cleavage site, were HP for experimentally infected chickens, and were thus characterized as HP AIV. These HA genes shared high amino acid identities with genes of other H5N1 viruses isolated in Asia during this period, but they were genetically distinct from those of H5N1 viruses isolated from poultry and humans in Vietnam during the early 2004 outbreaks. These viruses were not highly virulent for experimentally infected ducks, mice, or ferrets. These results establish that HP H5N1 viruses with properties similar to viruses isolated in Hong Kong and mainland China circulated in Vietnam as early as 2001, suggest a common source for H5N1 viruses circulating in these Asian countries, and provide a framework to better understand the recent widespread emergence of HP H5N1 viruses in Asia.


[Forensic and medical aspects of lethality from thromboembolytic complications of trauma, diseases and certain pathological conditions].
A total of 743 lethal outcomes of thromboembolytic complications of trauma, diseases and certain pathological conditions as observed in 1999-2001 and in the three quarters of 2002 were studied. The undertaken analysis confirmed two factors provoking the pathological thrombosis, i.e. 1. Pathological changes observed in the surface vascular wall preconditioned by mechanical damages, atherosclerotic process and aging; and 2. A slower blood flow due to an impaired blood circulation, a forced positioning and to hypodynamics. While deciding on a possibility of a direct cause-effect relation between past traumas, surgeries, poisonings and death of thromboembolism of the pulmonary arteries (TEPA), such relation can be mentioned only on rare occasions. It is more often the case that an indirect, mediated relationship is found, when TERA evolves due to an unfavorable combination of risk factors, i.e. a forced immobility, changing coagulated blood system, impaired blood vessels etc.


Effects of platelet-rich plasma on the clinical outcomes and cartilage thickness in patients with knee osteoarthritis.
The interest in biological treatments that have the potential to modify cartilage biology has gradually increased in recent years. The aim of our study was to investigate the effects of intra-articular platelet-rich plasma (IA-PRP) injections on the femoral cartilage thickness, pain, functional status, and quality of life of patients with knee osteoarthritis. A total of 71 patients (109 knees) with knee osteoarthritis who were administered IA-PRP injections twice with two-week intervals were included in this study. The resting and activity pain values measured using a Visual Analogue Scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, the Lequesne index scores, and the quality of life scores measured using Short Form-36 (SF-36) were recorded before treatment and at 1 month, 3 months, and 6 months after treatment. The femoral cartilage thickness was measured via ultrasonography before treatment, and at 3-month and 6-month follow ups. Obtained results were analyzed by the Wilcoxon signed rank test. The mean age of the patients was 47.4 ± 10.4 years old. The resting and activity pain scores were significantly decreased at 1-month, 3-month and 6-month follow ups when compared to the pre-injection values (p< 0.05). Significant reductions were found in the Lequesne index and WOMAC pain, stiffness, and function scores at 1, 3, and 6 months (p< 0.05), while a significant increase was detected in the third month scores when compared to the first month. Significant improvements were determined in the physical functioning, physical role, pain, general health, and emotional role sub-scores during the 6-month period (p< 0.05). However, there was no significant difference with regard to the cartilage thickness at the follow ups (p> 0.05). The results of our study indicated that the IA-PRP injections improved the pain, stiffness, physical functioning, and quality of life of knee osteoarthritis patients; however, they did not seem to affect the cartilage thickness during the 6-month follow up period.


Photoperiodic and circadian bifurcation theories of depression and mania.
Seasonal effects on mood have been observed throughout much of human history. Seasonal changes in animals and plants are largely mediated through the changing photoperiod (i.e., the photophase or duration of daylight). We review that in mammals, daylight specifically regulates SCN (suprachiasmatic nucleus) circadian organization and its control of melatonin secretion. The timing of melatonin secretion interacts with gene transcription in the pituitary pars tuberalis to modulate production of TSH (thyrotropin), hypothalamic T3 (triiodothyronine), and tuberalin peptides which modulate pituitary production of regulatory gonadotropins and other hormones. Pituitary hormones largely mediate seasonal physiologic and behavioral variations. As a result of long winter nights or inadequate illumination, we propose that delayed morning offset of nocturnal melatonin secretion, suppressing pars tuberalis function, could be the main cause for winter depression and even cause depressions at other times of year. Irregularities of circadian sleep timing and thyroid homeostasis contribute to depression. Bright light and sleep restriction are antidepressant and conversely, sometimes trigger mania. We propose that internal desynchronization or bifurcation of SCN circadian rhythms may underlie rapid-cycling manic-depressive disorders and perhaps most mania. Much further research will be needed to add substance to these theories.


Designing a disease management program: how to get started.
To successfully design and implement disease management programs, clinicians must understand the disease's natural course and cost drivers, base the diagnosis and treatment on the disease process and not the reimbursement schedules, educate and reinforce compliance to improve treatment outcomes, and focus on commonly occurring and costly chronic diseases. This article describes a 7-step process for developing a disease management program based on those concepts. The changing role and functions of the P & T Committee in disease management programs are also presented.


Metabolism configures immune response across multi-systems: Lessons from COVID-19.
Several studies over the last decade demonstrate the recruitment of immune cells, increased inflammatory cytokines, and chemokine in patients with metabolic diseases, including heart failure, parenchymal inflammation, obesity, tuberculosis, and diabetes mellitus. Metabolic rewiring of immune cells is associated with the severity and prevalence of these diseases. The risk of developing COVID-19/SARS-CoV-2 infection increases in patients with metabolic dysfunction (heart failure, diabetes mellitus, and obesity). Several etiologies, including fatigue, dyspnea, and dizziness, persist even months after COVID-19 infection, commonly known as Post-Acute Sequelae of CoV-2 (PASC) or long COVID. A chronic inflammatory state and metabolic dysfunction are the factors that contribute to long COVID. Here, this study explores the potential link between pathogenic metabolic and immune alterations across different organ systems that could underlie COVID-19 and PASC. These interactions could be utilized for targeted future therapeutic approaches.


Capsule Endoscopy in Inflammatory Bowel Disease: Panenteric Capsule Endoscopy and Application of Artificial Intelligence.
Video capsule endoscopy (VCE) of the small-bowel has been proven to accurately diagnose small-bowel inflammation and to predict future clinical flares among patients with Crohn's disease (CD). In 2017, the panenteric capsule (PillCam Crohn's system) was introduced for the first time, enabling a reliable evaluation of the whole small and large intestines. The great advantage of visualization of both parts of the gastrointestinal tract in a feasible and single procedure, holds a significant promise for patients with CD, enabling determination of the disease extent and severity, and potentially optimize disease management. In recent years, applications of machine learning, for VCE have been well studied, demonstrating impressive performance and high accuracy for the detection of various gastrointestinal pathologies, among them inflammatory bowel disease lesions. The use of artificial neural network models has been proven to accurately detect/classify and grade CD lesions, and shorten the VCE reading time, resulting in a less tedious process with a potential to minimize missed diagnosis and better predict clinical outcomes. Nevertheless, prospective, and real-world studies are essential to precisely examine artificial intelligence applications in real-life inflammatory bowel disease practice.


Model for the alpha and beta shear-mechanical properties of supercooled liquids and its comparison to squalane data.
This paper presents data for supercooled squalane's frequency-dependent shear modulus covering frequencies from 10 mHz to 30 kHz and temperatures from 168 K to 190 K; measurements are also reported for the glass phase down to 146 K. The data reveal a strong mechanical beta process. A model is proposed for the shear response of the metastable equilibrium liquid phase of supercooled liquids. The model is an electrical equivalent-circuit characterized by additivity of the dynamic shear compliances of the alpha and beta processes. The nontrivial parts of the alpha and beta processes are each represented by a "Cole-Cole retardation element" defined as a series connection of a capacitor and a constant-phase element, resulting in the Cole-Cole compliance function well-known from dielectrics. The model, which assumes that the high-frequency decay of the alpha shear compliance loss varies with the angular frequency as ω-1/2, has seven parameters. Assuming time-temperature superposition for the alpha and beta processes separately, the number of parameters varying with temperature is reduced to four. The model provides a better fit to the data than an equally parametrized Havriliak-Negami type model. From the temperature dependence of the best-fit model parameters, the following conclusions are drawn: (1) the alpha relaxation time conforms to the shoving model; (2) the beta relaxation loss-peak frequency is almost temperature independent; (3) the alpha compliance magnitude, which in the model equals the inverse of the instantaneous shear modulus, is only weakly temperature dependent; (4) the beta compliance magnitude decreases by a factor of three upon cooling in the temperature range studied. The final part of the paper briefly presents measurements of the dynamic adiabatic bulk modulus covering frequencies from 10 mHz to 10 kHz in the temperature range from 172 K to 200 K. The data are qualitatively similar to the shear modulus data by having a significant beta process. A single-order-parameter framework is suggested to rationalize these similarities.


Raf-1 regulates Rho signaling and cell migration.
Raf kinases relay signals inducing proliferation, differentiation, and survival. The Raf-1 isoform has been extensively studied as the upstream kinase linking Ras activation to the MEK/ERK module. Recently, however, genetic experiments have shown that Raf-1 plays an essential role in counteracting apoptosis, and that it does so independently of its ability to activate MEK. By conditional gene ablation, we now show that Raf-1 is required for normal wound healing in vivo and for the migration of keratinocytes and fibroblasts in vitro. Raf-1-deficient cells show a symmetric, contracted appearance, characterized by cortical actin bundles and by a disordered vimentin cytoskeleton. These defects are due to the hyperactivity and incorrect localization of the Rho-effector Rok-alpha to the plasma membrane. Raf-1 physically associates with Rok-alpha in wild-type (WT) cells, and reintroduction of either WT or kinase-dead Raf-1 in knockout fibroblasts rescues their defects in shape and migration. Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration.


The Renaissance of Unicompartmental Knee Arthroplasty appears rational - A radiograph-based comparative Study on adverse Events and patient-reported Outcomes in 353 TKAs and 98 UKAs.
Total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) are both considered suitable for antero-medial osteoarthritis and spontaneous osteonecrosis of the knee. National registry data are consistent in showing higher revision rates for UKA. Adequately adjusted, these findings may be challenged by differences in adverse events and patient-reported outcomes, as both can have serious long-term implications. Based on preoperative radiographs, the aim was to retrospectively compare the two principle surgeries in these respects. All TKA procedures in 2016 in one Swedish county council were, according to certain radiograph-based consensus criteria, visually evaluated for medial UKA suitability. Then, using different regression models, they were compared with the corresponding medial UKAs performed in 2015-2017 regarding complications and patient-reported outcomes one year after surgery. The UKA group showed an 82% reduced risk (OR 0.2; 95% CI 0.0-0.6) of any complications, whereas the 55% reduced risk of severe complication did not reach statistical significance (OR 0.5; 95% CI 0.1-2.1). These findings corresponded in high-volume surgeries to an absolute complication rate of 0% in the UKA group and 10% in the TKA group (p = 0.005) and to a severe complication rate of 0% and 5% respectively (p = 0.05). Though no differences were seen in any general patient-reported outcomes, the pain and function based OMERACT-OARSI responder criteria indicated in both around a 60% better chance of any response (OR 1.6 CI % 0.6-4.5) and a high response (OR 1.6; 95% CI 0.7-3.4) in the UKA group. No differences were shown in patient-reported outcomes but a clear difference in risk of complications, favoring the UKA procedure.


Norwegian Clinicians' Experiences of Learnability and Usability of SCID-II, SCID-5-PD and SCID-5-AMPD-I Interviews: A Sequential Multi-Group Qualitative Approach.
The DSM-5 presents two competing diagnostic frameworks for personality disorders: the standard categorical model and the Alternative Model of Personality Disorders (AMPD). The AMPD was initially criticized for being too complex and theory laden for clinical implementation. Though inter-rater reliability studies have contested initial claims of the model's complexity, little attention has been paid to how clinicians experience the usability and learnability of either model. We interviewed twenty Norwegian clinicians about their experiences with either the SCID-II/5-PD (n = 9), SCID-5-AMPD-I (n = 8), or both (n = 3). Separate thematic analyses were conducted for SCID-II/5-PD and SCID-5-AMPD-I groups, and group themes were compared. We identified four themes for each group, relating to required skills, training, challenges and information gained through the interview. We found that training and clinical experience were considered to be important for both interviews. Moreover, the SCID-5-AMPD-I was considered to rely more explicitly on theory specific to the development and content of the AMPD model in general and the LPFS specifically We also identified shared and unique challenges and shortcomings of each interview. We comment on how our findings relate to the debate surrounding the AMPD, and recommend development of clear training guidelines for both interviews.


Renal chloride channel, CLCN5, mutations in Dent's disease.
Dent's disease is an X-linked renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. Patients with Dent's disease may also suffer from rickets and other features of the renal Fanconi Syndrome. Patients may have mutations in the X-linked renal chloride channel gene, CLCN5, which encodes a 746-amino-acid protein with 12-13 transmembrane domains. We have investigated the 11 coding exons of CLCN5 for mutations in eight unrelated patients with Dent's disease. Leukocyte DNA was used for the polymerase chain reaction amplification of CLCN5 and the products analyzed for single-stranded conformational polymorphisms (SSCPs). Abnormal SSCPs were sequenced and revealed eight mutations. These consisted of three nonsense mutations (Arg34Stop, Arg648Stop, Arg704Stop), four deletions involving codons 40, 86, 157, and 241, and one acceptor splice consensus sequence mutation tgcag --> tgaag. The mutations were confirmed either by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis. In addition, an analysis of 110 alleles from 74 unrelated normal individuals demonstrated that the DNA sequence changes were not common polymorphisms. All of the mutations predict truncated chloride channels that are likely to result in a functional loss. Thus, our findings expand the spectrum of CLCN5 mutations associated with Dent's disease and the results will help to elucidate further the functional domains of this novel chloride channel.


Enterococcus xiangfangensis sp. nov., isolated from Chinese pickle.
A Gram-stain-positive bacterial strain, 11097(T), was isolated from traditional pickle in Heilongjiang Province, China. The bacterium was characterized using a polyphasic approach, including 16S rRNA gene sequence analysis, phenylalanyl-tRNA synthase (pheS) gene sequence analysis, RNA polymerase α subunit (rpoA) gene sequence analysis, fatty acid methyl ester (FAME) analysis, determination of DNA G+C content, DNA-DNA hybridization and an analysis of phenotypic features. Strain 11097(T) was phylogenetically related to Enterococcus devriesei, E. pseudoavium, E. viikkiensis, E. avium, E. malodoratus, E. gilvus and E. raffinosus. Strain 11097(T) had 99.1-99.9% 16S rRNA gene sequence similarities, 78.2-83.2% pheS gene sequence similarities and 93.8-96.6% rpoA gene sequence similarities with type strains of phylogenetically related species. Based upon polyphasic characterization data obtained in the present study, a novel species of the genus Enterococcus, Enterococcus xiangfangensis sp. nov., is proposed with the type strain 11097(T) ( = LMG 27495(T) = NCIMB 14834(T)).


Abdominal circumference in relation to body weight gain/loss in patients on chronic hemodialysis.
to determine a constant relationship between changes in abdominal circumference (in centimeter) and body weight (in kilogram) in chronic kidney disease (CKD) patients undergoing chronic hemodialysis. experimental-analytical study in patients with CKD on hemodialysis, using before and after treatment design at the Dialysis Unit of Cipto Mangunkusumo Hospital, Jakarta. The sample were selected consecutively. Weighing and abdominal circumference measurements were done at the time of before and after hemodialysis session on the same day. Repeated measurements were performed on different days in 104 subjects to achieve the target sample size of 676. Serum albumin level were also measured on the patients. there was a strong (r=0.838) and significant (p=0.000) correlation between mean body weight and mean abdominal circumferences before and after hemodialysis. In the calculation of the regression between the mean body weight before and after hemodialysis (X) with a mean abdominal circumference before and after hemodialysis (Y), regression formula: Y=34.94 + 0.84 X was obtained. There was no significant correlation between serum albumin levels (3.93±0.40 g/dL) and abdominal circumference before hemodialysis, abdominal circumference after hemodialysis, and the mean abdominal circumference before and after hemodialysis. prediction of weight changes in patients with CKD on chronic hemodialysis, can be measured through the abdominal circumference measurement before and after hemodialysis.


Phylogenetic and functional diversity of denitrifying bacteria isolated from various rice paddy and rice-soybean rotation fields.
Denitrifiers can produce and consume nitrous oxide (N(2)O). While little N(2)O is emitted from rice paddy soil, the same soil produces N(2)O when the land is drained and used for upland crop cultivation. In this study, we collected soils from two types of fields each at three locations in Japan; one type of field had been used for continuous cultivation of rice and the other for rotational cultivation of rice and soybean. Active denitrifiers were isolated from these soils using a functional single-cell isolation method, and their taxonomy and denitrifying properties were examined. A total of 110 denitrifiers were obtained, including those previously detected by a culture-independent analysis. Strains belonging to the genus Pseudogulbenkiania were dominant at all locations, suggesting that Pseudogulbenkiania denitrifiers are ubiquitous in various rice paddy soils. Potential denitrifying activity was similar among the strains, regardless of the differences in taxonomic position and soil of origin. However, relative amounts of N(2) in denitrification end products varied among strains isolated from different locations. Our results also showed that crop rotation had minimal impact on the functional diversity of the denitrifying strains. These results indicate that soil and other environmental factors, excluding cropping systems, could select for N(2)-producing denitrifiers.


#anatomymcq-A pilot study on using the Twitter survey tool as a formative assessment strategy.
This article was migrated. The article was marked as recommended. Background: Various social media portals, such as Facebook, Twitter, and YouTube, are emerging fast as effective platforms in anatomy education. Interestingly, the survey tool of Twitter can be utilized to develop multiple-choice questions, where the students may cast their votes in favor of the correct option. To assess the utility of the tool, a study was undertaken over fourteen weeks (twelve weeks of tutorials and two weeks of study break before the end-of-term examination) during the second semester of the 2016-2017 academic year in the University College Dublin School of Veterinary Medicine under voluntary and anonymous participation. Methods: One survey with four alternatives and marked with #anatomymcq was posted on each day of the week, while the correct answer was revealed the following day, also marked with the #anatomymcq-thus, a total of 67 such surveys broadly classifiable under the following topics: gastrointestinal system (n=14), urinary system (n=12), comparative anatomy (n=10), embryology (n=10), reproductive system (n=14) and applied anatomy (n=7) were tweeted. Results: Altogether 263 votes were received (highest in the weeks 7 and 8) for the 67 surveys in the following order: GI system (6.50 votes/survey) > urinary system (4.33 votes/survey) > comparative anatomy (3.60 votes/survey) > embryology (2.90 votes/survey) > reproductive system (2.64 votes/survey) > applied anatomy (2.57 votes/survey). The average daily impressions for the surveys were significantly ( p<0.05) higher than the first week, while the weekly mean engagement rate grew from the first week as well. The weekly total number of hashtag clicks also increased. The student feedback was positive on the exercise. Conclusions: The integrated data highlight the potential of such a tool while identifying its strengths and weaknesses and was able to provide an interactive tool to engage students outside the formal teaching hours while facilitating student learning and engagement.


TennCare: Tennessee's answer to runaway Medicaid costs.
TennCare was implemented in Tennessee on January 1, 1994, as the state's replacement program for Medicaid. Created through a demonstration waiver under Section 1115(a) of the Social Security Act, TennCare is unlike any other state Medicaid program in the nation because it includes coverage of uninsured and uninsurable Tennesseans. By contracting with managed care organizations (MCOs) to administer the Medicaid benefit package to TennCare enrollees, the state virtually privatized the program and dramatically shifted the state's responsibility from one of total administration to an oversight function only. Amid provider lawsuits, MCO contract controversy, and general chaos surrounding the new program, the implementation of TennCare created one of the most significant health care events in the state's history. This article provides an overview of the TennCare program and its impact on enrollees, providers, and the state budget.


Molecular mapping and identification of quantitative trait loci for domestication traits in the field cress (Lepidium campestre L.) genome.
Lepidium campestre (L.) or field cress is a multifaceted oilseed plant, which is not yet domesticated. Moreover, the molecular and genetic mechanisms underlying the domestication traits of field cress remain largely elusive. The overarching goal of this study is to identify quantitative trait loci (QTL) that are fundamental for domestication of field cress. Mapping and dissecting quantitative trait variation may provide important insights into genomic trajectories underlying field cress domestication. We used 7624 single nucleotide polymorphism (SNP) markers for QTL mapping in 428 F2 interspecific hybrid individuals, while field phenotyping was conducted in F2:3 segregating families. We applied multiple QTL mapping algorithms to detect and estimate the QTL effects for seven important domestication traits of field cress. Verification of pod shattering across sites revealed that the non-shattering lines declined drastically whereas the shattering lines increased sharply, possibly due to inbreeding followed by selection events. In total, 1461 of the 7624 SNP loci were mapped to eight linkage groups (LGs), spanning 571.9 cM map length. We identified 27 QTL across all LGs of field cress genome, which captured medium to high heritability, implying that genomics-assisted selection could deliver domesticated lines in field cress breeding. The use of high throughput genotyping can accelerate the process of domestication in novel crop species. This is the first QTL mapping analysis in the field cress genome that may lay a foundational framework for positional or functional QTL cloning, introgression as well as genomics-assisted breeding in field cress domestication.


Non-stress-related factors associated with maternal corticotrophin-releasing hormone (CRH) concentration.
During pregnancy, most maternal corticotrophin-releasing hormone (CRH) is secreted by the placenta, not the hypothalamus. Second trimester maternal CRH concentration is robustly associated with the subsequent risk of preterm birth, and it is often assumed that physiological and/or psychological stress stimulates placental CRH release. Evidence supporting the latter assumption is weak, however, and other factors affecting maternal CRH have received little attention from investigators. We carried out a case-control study nested within a large, multicentre prospective cohort of pregnant women to examine potential 'upstream' factors associated with maternal CRH concentration measured at 24-26 weeks of gestation. The predictors studied included maternal age, parity, birthplace (as a proxy for ethnic origin), pre-pregnancy body mass index, height, smoking, bacterial vaginosis and vaginal fetal fibronectin (FFN) concentration. Women with high (above the median) plasma CRH concentration were significantly less likely to have been born in Sub-Saharan Africa or the Caribbean, less likely to be overweight or obese, and more likely to be smokers. Associations with maternal birthplace and BMI persisted in logistic regression analyses controlling for potential confounding variables and when restricted to term controls. A strong (but imprecise and statistically non-significant) association was also observed with high vaginal FFN concentration. Further studies are indicated both in animal models and human populations to better understand the biochemical and physiological pathways to CRH secretion and their aetiological role, if any, in preterm birth.


Radiofrequency ablation-assisted liver resection: a step toward bloodless liver resection.
Liver resection is currently the most efficient curative approach for a wide variety of liver tumors. The application of modern techniques and new surgical devices has improved operative outcomes. Radiofrequency ablation is used more often for liver parenchymal transection. This study aimed to assess the efficacy and safety of radiofrequency ablation-assisted liver resection. A retrospective study of 145 consecutive patients who underwent radiofrequency ablation-assisted liver resection was performed. Intraoperative blood loss, need for transfusion or intraoperative Pringle maneuver, the duration of liver parenchymal transection, perioperative complications, and postoperative morbidity and mortality were all evaluated. Fifty minor and ninety-five major liver resections were performed. The mean intraoperative blood loss was 251 mL, with a transfusion rate of 11.7%. The Pringle maneuver was necessary in 12 patients (8.3%). The mean duration for parenchymal transection was 51.75 minutes. There were 47 patients (32.4%) with postoperative complications. There is no mortality within 30 days after surgery. Radiofrequency ablation-assisted liver resection permits both major and minor liver resections with minimal blood loss and without occlusion of hepatic inflow. Furthermore it decreases the need for blood transfusion and reduces morbidity and mortality.


Structure, function and control of complement C5 and its proteolytic fragments.
As part of the innate immune system, the complement system recognises a wide range of non-self structures present on pathogens or altered self cells. Its activation elicits proteolytic cascades which eventually results in the cleavage of the C5 protein into two fragments, C5a and C5b. The small anaphylatoxin C5a induces a variety of biological responses upon binding to the 7TM receptors C5aR and the C5L2, while the large C5b fragment nucleates formation of the membrane attack complex capable of killing susceptible pathogens by the formation of a pore structure in association with complement components C6, C7, C8, and C9. A number of regulatory molecules help to control C5 mediated immune responses towards host cells, but in several major inflammatory conditions including sepsis and arthritis, C5a is believed to contribute significantly to disease etiology. Inhibition of membrane attack complex assembly is already approved for treatment of paroxysmal nocturnal haemoglobinuria and atypical hemolytic uremic syndrome. A number of recent crystal structures have provided a comprehensive insight into the architecture and properties of intact C5 and its fragments, and how pathogens interfere with their function. Here we review the functional and structural aspects of C5 and its fragments, the pathological conditions associated with them, and strategies employed by pathogens to interfere with the biological function of C5. Structural insight and elucidation of evasion strategies employed by pathogens present a unique opportunity for promoting the development of novel selective C5 inhibitors with therapeutic applications.


Correction of velopharyngeal insufficiency with furlow palatoplasty.
To evaluate the authors' experience with Furlow palatoplasty for velopharyngeal insufficiency. Review of 8 cases over a 3-year period. Regional private practice hospital affiliated with a teaching university. Eight patients aged 4 to 14 years with symptoms and signs of velopharyngeal insufficiency underwent Furlow palatoplasty. Four patients had submucous or soft palate clefts without previous intervention. Four patients had undergone previous surgery for cleft palate. All patients underwent Furlow palatoplasty. Fiberoptic nasopharyngeal examination and speech analysis. Seven of 8 patients exhibited good palate closure and marked improvement in speech. One patient exhibited good closure but had mild nasal emission and hypernasality, which responded to speech therapy after surgery. Furlow palatoplasty is a useful technique for the correction of velopharyngeal insufficiency in selected patients.


The Role of Culture of Origin on the Effectiveness of a Parents-Involved Intervention to Prevent Substance Use Among Latino Middle School Youth: Results of a Cluster Randomized Controlled Trial.
The purpose of this study was to assess the combined effectiveness of a parenting intervention, Families Preparing the New Generation (FPNG), and a youth curriculum, keepin' it REAL (kiR), on substance use prevention for middle school students in a large urban metro area of the southwest USA. The study aimed to generate usable knowledge on what works in adolescent substance use prevention and how it works best-a combined parent and youth programming or parent-only programming. A total of 532 adolescents in the 7th grade from 19 participating middle schools were randomly assigned into three intervention conditions: parent-youth (PY), parent-only (PO), and comparison (C). This article focuses on the comparison between PY and PO in order to determine which intervention strategy works best to reduce adolescent substance use including alcohol, inhalant, cigarette, and marijuana uses. A generalized estimating equation (GEE) model examined the longitudinal data. The results for alcohol use show that PO yielded better results than PY and that PY outperformed C after 20 months. Further, PO showed a decreasing trajectory in any substance use over time since the implementation of the intervention. The effect sizes based on Cohen's h indicate small effects in any substance use and alcohol use for PO condition and smaller effects for the PY condition. These findings have implications for the design of future culturally specific parenting and youth prevention interventions with Latino families.


Nepalese undergraduate nursing students' perceptions of the clinical learning environment, supervision and nurse teachers: A questionnaire survey.
Clinical practice enables nursing students to acquire essential professional skills, but little is known about nursing students' perceptions of the clinical learning environment (CLE) in Nepal. To examine Nepalese nursing students' perceptions regarding the CLE and supervision. A cross-sectional questionnaire design was used. Government and private hospitals in Nepal where the undergraduate nursing college students undertook their clinical practice. Students with clinical practice experience were recruited from years 2-4 of the B.Sc. nursing program in Nepal (n=350). The final sample comprised 263 students. A self-administered questionnaire including demographic characteristics, latest clinical practice site, and general satisfaction was administered February-March 2014. The previously validated Clinical Learning Environment, Supervision and Nurse Teacher evaluation scale was used in the questionnaire. The analytical approach used exploratory factor analysis, assessments of the scale and sub-dimension reliability, correlations of factors between scale sub-dimensions, and multiple regression analysis. Students' practicum satisfaction level at government hospitals was significantly higher than those at private hospitals (p<0.0001). Five factors explained 85.7% of the variance, with minor factorial structure differences compared with the original scale. Reliability was confirmed (Cronbach's alpha=0.93 for total scale, 0.76-0.92 for sub-dimensions). Inter-correlations between the five original sub-dimensions were 0.27-0.68 (p<0.0001). Students undertaking their practicum in private hospitals evaluated their clinical placements significantly more negatively on most sub-dimensions than those in government hospitals. Multiple regression analysis revealed a significant positive relationship between satisfaction and pedagogical atmosphere (p<0.0001). This is the first study to investigate nursing students' perceptions of the CLE in undergraduate nursing programs in Nepal. Students were satisfied with the CLE overall, but satisfaction varied by practicum hospital sector. The most influential factor explaining satisfaction was pedagogical atmosphere.


HIV-gp120 induced cell death in hematopoietic progenitor CD34+ cells.
Haematologic abnormalities accompany the majority of HIV-1 infections. At present it is unclear whether this is due directly to HIV infection of hematopoietic progenitor cells, or whether this results from an indirect mechanism secondary to HIV infection. Here we provide evidence for an indirect mechanism, whereby hematopoietic progenitor cells undergo HIV gp120-induced apoptosis (programmed cell death) even in the absence of HIV infection. Freshly isolated, purified human hematopoietic progenitor CD34+ cells, derived from both umbilical cord blood and bone marrow, co-expressed the CD4 marker at low density on their surface. Although these CD34+CD4+ cells theoretically should be capable of productive infection by HIV, we found that HIV-IIIB could not establish productive infection in these cells. Nonetheless, gp120 from IIIB could bind the cells. Thus, binding of gp120 did not correlate with infectivity. Furthermore, binding of gp120 was a specific event, leading to apoptosis upon crosslinking with anti-gp120 through a fas-dependent mechanism. If apoptosis is also observed in vivo even in uninfected hematopoietic cells, this could contribute significantly to the impairment in hematopoietic cell number and function. Our data suggest a novel indirect mechanism for depletion of CD34+ and CD34+-derived cells even in the absence of productive viral infection of these cells.


Isolation and characterization of Wad Medani virus obtained in the tuva Republic of Russia.
Wad Medani virus (WMV) belongs to the genus Orbivirus and is a poorly studied arbovirus with unclear medical significance. Presently, a limited number of WMV strains are characterized and available in NCBI GenBank, some isolated many years ago. A new WMV strain was isolated in 2012 from Dermacentor nuttalli ticks collected from sheep in the Tuva Republic, Russia, and sequenced using high-throughput methods. Complete coding sequences were obtained revealing signs of multiple intersegment reassortments. These point to a high variability potential in WMV that may lead to the formation of strains with novel properties. These new data on WMV can promote better understanding of: ecological features of its circulation; relationships within the genus Orbivirus; and the medical significance of the virus.


General anesthesia improves fetal cerebral oxygenation without evidence of subsequent neuronal injury.
Anesthetic exposure during pregnancy is viewed as a relatively routine medical practice. However, recent rodent studies have suggested that common anesthetic agents can damage the developing brain. Here we assessed this claim in a higher order species by exposing previously instrumented near-term pregnant sheep at gestational day 122 (+/-1) to a combination of midazolam, sodium thiopental, and isoflurane at clinically relevant doses and means of anesthetic delivery (i.e., active ventilation). Four hours of maternal general anesthesia produced an initial increase in fetal systemic oxygenation and a sustained increase in fetal cerebral oxygenation, as determined by in utero near-infrared spectroscopy. Postexposure monitoring failed to identify changes in physiologic status that could be injurious to the fetal brain. Finally, through the histologic assessment of noninstrumented sheep at the same gestational time point, we found no evidence for a direct fetal neuro-toxic effect of our triple-drug regimen. Collectively, these results appear to corroborate the presumed safety of inhalational anesthetic use during pregnancy.


Enhancing Diffusion MRI Measures By Integrating Grey and White Matter Morphometry With Hyperbolic Wasserstein Distance.
In order to improve the preclinical diagnose of Alzheimer's disease (AD), there is a great deal of interest in analyzing the AD related brain structural changes with magnetic resonance image (MRI) analyses. As the major features, variation of the structural connectivity and the cortical surface morphometry provide different views of structural changes to determine whether AD is present on presymptomatic patients. However, the large scale tensor-valued information and relatively low imaging resolution in diffusion MRI (dMRI) have created huge challenges for analysis. In this paper, we propose a novel framework that improves dMRI analysis power by fusing cortical surface morphometry features from structural MRI (sMRI). We first compute the hyperbolic harmonic maps between cortical surfaces with the landmark constraints thus to precisely evaluate surface tensor-based morphometry. Meanwhile, the graph-based analysis of structural connectivity derived from dMRI is conducted. Next, we fuse these two features via the optimal mass transportation (OMT) and eventually the Wasserstein distance (WD) based single image index is computed as a potential clinical multimodality imaging score. We apply our framework to brain images of 20 AD patients and 20 matched healthy controls, randomly chosen from the Alzheimer's Disease Neuroimaging Initiative (AD-NI2) dataset. Our preliminary experimental results of group classification outperformed those of some other single dMRI-based features, such as regional hippocampal volume, mean scores of fractional anisotropy (FA) and mean axial (MD). The novel image fusion pipeline and simple imaging score of structural changes may benefit the preclinical AD and AD prevention research.


Experiments and simulations of ion-enhanced interfacial chemistry on aqueous NaCl aerosols
A combination of experimental, molecular dynamics, and kinetics modeling studies is applied to a system of concentrated aqueous sodium chloride particles suspended in air at room temperature with ozone, irradiated at 254 nanometers to generate hydroxyl radicals. Measurements of the observed gaseous molecular chlorine product are explainable only if reactions at the air-water interface are dominant. Molecular dynamics simulations show the availability of substantial amounts of chloride ions for reaction at the interface, and quantum chemical calculations predict that in the gas phase chloride ions will strongly attract hydroxl radicals. Model extrapolation to the marine boundary layer yields daytime chlorine atom concentrations that are in good agreement with estimates based on field measurements of the decay of selected organics over the Southern Ocean and the North Atlantic. Thus, ion-enhanced interactions with gases at aqueous interfaces may play a more generalized and important role in the chemistry of concentrated inorganic salt solutions than was previously recognized.


Impaired fibrinolysis in retinal vein occlusion: a role for genetic determinants of PAI-1 levels.
Few and contrasting data are available on the presence of a thrombophilic state in patients with retinal vein occlusion (RVO), and we have previously demonstrated a role of elevated PAI-1 activity as a risk factor for this condition. The present study was undertaken to investigate whether PAI 4G/5G and ACE I/D polymorphisms are independent risk factors for RVO and whether they account for elevated PAI-1 activity levels. We studied 112 RVO patients (52 males and 60 females; range 18-83 years; median age 60 years) and 112 healthy subjects (52 males and 60 females; range 20-84 years; median age 57 years). PAI-1 activity was determined by a chromogenic assay and ACE I/D and PAI-1 4G/5G polymorphisms by polymerase chain reaction (PCR) and restriction length fragment polymorphism (RLFP) methods. Elevated PAI-1 activity (above 95(th) percentile of the controls) was significantly associated with RVO at multivariate analysis after adjustment for age, sex, traditional cardiovascular risk factors and haemostasis-related risk factors (OR = 4.93, 95% CI 1.70-14.30; p = 0.003). The homozygosity for ACE DD was found to be an independent risk factor for RVO at multivariate analysis (OR = 1.98, 95% CI 1.01-3.83; p = 0.049), whereas no significant association between homozygosity for PAI-1 4G4G and risk of RVO was observed. Subjects carrying both ACE DD genotype and PAI-1 4G4G genotype showed an increased risk for RVO at multivariate analysis (OR = 4.82, 95% CI 1.89-12.29; p = 0.001). In 45/112 patients without the established risk factors for RVO (hyper-tension, hypercholesterolemia and diabetes) or characteristics known to be associated to increased PAI-1 activity (overweight, hypertriglyceridemia, and smoking habit) the contemporary presence of ACE DD and PAI-1 4G4G genotype was significantly associated with a risk for RVO (OR = 8.26, 95% CI 1.18-57.92; p = 0.034). In conclusion, in our study: 1-indicates that ACE DD genotype is a risk factor for RVO in the whole group of patients, and in the subgroup of patients without the established risk factors for RVO or characteristics influencing the PAI-1 activity, when associated to PAI-1 4G4G genotype, and 2-confirms the role of hypofibrinolysis, documented by high levels of PAI-1 activity, in the occurrence of patients with RVO.


Magnetic and catalytic properties of Cu0.5Zn0.5Fe2O4 nanocrystallite powders.
Cu0.5Zn0.5Fe2O4 nanocrystallite powders (average size 13 nm) were synthesized from Cu-Zn spent catalyst (fertilizers) industries and ferrous sulfate wastes formed during iron and steel making. Cu-Zn catalyst (22.4% Cu and 26.4% Zn) was chemically treated with sulfuric acid at temperature 80 degrees C for 1 hr for the complete dissolving of copper and zinc into sulfate solution, then the produced solution was mixed with stoichiometric ratio of ferrous sulfate and the mixture was chemically precipitated as hydroxides followed by hydrothermal processing. The parameters affecting the magnetic properties and crystallite size of the produced ferrites powder e.g., temperature, time, and pH were systemically studied. X-ray diffraction analysis was used in order to determine the average crystallite size and phase identifications of the produced powder. The magnetic properties were studied by vibrating sample magnetometry. The results showed that the average crystallite size of the powder decreased for the ferrites powder formed at 150 degrees C and then increased by increasing the temperature to 200 degrees C. Interestingly, the saturation magnetization (Bs), remanent magnetization (Br) and coercive force (Hc) were 25.03 emu/g, 0.71 emu/g, and 4.83 Oe, respectively at hydrothermal temperature 150 degrees C for 24 hr and changed to 16.38 emu/g, 0.3864 emu/g, and 5.2 Oe at 150 degrees C and 72 hr. The produced nanoferrite powders are used for studying the catalytic activity of CO conversion to CO2 at different temperatures, pH and times. The maximum conversion (82%) is obtained at temperature 150 degrees C for 24 hrs and pH 12.


[Obesity as a risk factor in the development of cancer].
According to the World Health Organization, every year about 3.4 million adults die of consequences related to overweight or obesity. People with a Body Mass Index above 30 are more likely to express certain diseases, including some types of cancer. In this narrative review, we assess the role of adipose tissue as a modulator of the endocrine system and facilitator of chronic subclinical inflammation. We discuss how obesity can induce a suitable micro environment for the development of tumors, mainly by enhancing the levels of oxidative stress and the concentrations of hormones such as leptin, insulin and prolactin. We conclude that all together, these factors increase the probability of cancer development.