An In Vitro Evaluation of the Effects of Air-Polishing Powders on Sound and Demineralised Enamel.
To evaluate the effects of two air-polishing powders, during orthodontic treatment, on the surface roughness of sound and demineralised enamel. Forty-two caries-free human molars were collected, and the enamel surfaces were flattened and polished. Teeth were assigned to two groups (n = 21 each), a sound- and a demineralised-enamel group (subjected to pH-cycling over 2 weeks to create artificially induced white spot-like lesions). Within each group, teeth were further assigned to three groups (n = 7 each), air polished with either sodium bicarbonate, erythritol, or a negative control (water). Each sample was treated for 5 and 150 s. The average surface roughness (Ra) for each sample was measured using white-light-sensor profilometry. On sound enamel, the Ra was roughly 0.17 ± 0.07 μm. After 150 s of air polishing, the Ra increased with erythritol (by 0.28 μm), and even more so with bicarbonate treatment (by 0.68 μm) (p < 0.01). On demineralised enamel, the Ra was roughly 0.79 ± 0.56 μm. The Ra increased after 5 s of air-polishing treatment similarly with erythritol and bicarbonate powders (by 1.03 μm and 1.04 μm, respectively) (p = 0.025), and even more after 150 s (by 2.48 μm and 2.49 μm, respectively) (p < 0.001). On white spot lesions, one should be aware that enamel surface roughness will increase with both erythritol and bicarbonate air-polishing powders, especially with longer exposure times.


Novel (glycerol)borate-based ionic liquids: an experimental and theoretical study.
A series of newly designed (glycerol)borate based ionic liquids were synthesized and characterized. The synthesis of these ionic liquids involves, first, the preparation of the bis(glycerol)boric acid(s) followed by neutralization with the appropriate base, [cat]OH. Ionic liquids bearing inorganic (Li(+), Na(+), K(+)) or organic cations have been prepared and characterized. The ability of the bis(glycerol)borate anions to undergo dissociation reaction in the presence of water, depending on cation nature, was investigated by NMR. Theoretical calculations were also performed to evaluate the relative stability of the possible bis(glycerol)borate isomers as nude ions or as ion pairs with Li(+), Na(+), and H(+). Important information about the structural features of H[Gly(2)B] useful to rationalize the chemical behavior have been obtained.


How the Object of Affect Guides its Impact.
In this article, we examine how affect influences judgment and thought, but also how thought transforms affect. The general thesis is that the nature and impact of affective reactions depends largely on their objects. We view affect as a representation of value, and its consequences as dependent on its object or what it is about. Within a review of relevant literature and a discussion of the nature of emotion, we focus on the role of the object of affect in governing both the nature of emotional reactions and the impact of affect and emotion on cognition and action. Although emotion is always about the here and now, the capacity for abstract thought means that the human here and now includes imagination as well as perception. Indeed, the hopes and fears that dominate human lives often involve things only imagined.


Effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 pathway.
This study aimed to investigate the effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 signaling pathway. A total of 43 adult female Wistar rats were selected and injected with HeLa cells in the caudal vein to construct a rat model of cervical cancer. All model rats were randomly divided into the radiotherapy group ( n = 31) and the control group ( n = 12). The immunophenotype of Treg cells was detected by the flow cytometry. The protein expressions of EBI3, PD-1, and PD-L1 in cervical cancer tissues were tested by the streptavidin-peroxidase method. HeLa cells in the logarithmic growth phase were divided into four groups: the blank, the negative control group, the EBI3 mimics group, and the EBI3 inhibitors group. Western blotting was used to detect PD-1 and PD-L1 protein expressions. MTT assay was performed to measure the proliferation of Treg cells. Flow cytometry was used to detect cell cycle and apoptosis, and CD4+/CD8+ T cell ratio in each group. Compared with before and 1 week after radiotherapy, the percentages of CD4+T cells and CD8+T cells were significantly decreased in the radiotherapy group at 1 month after radiotherapy. Furthermore, down-regulation of EBI3 and up-regulation of PD-1 and PD-L1 were observed in cervical cancer tissues at 1 month after radiotherapy. In comparison to the blank and negative control groups, increased expression of EBI3 and decreased expressions of PD-1 and PD-L1 were found in the EBI3 mimics group. However, the EBI3 inhibitors group had a lower expression of EBI3 and higher expressions of PD-1 and PD-L1 than those in the blank and negative control groups. The EBI3 mimics group showed an increase in the optical density value (0.43 ± 0.05), while a decrease in the optical density value (0.31 ± 0.02) was found in the EBI3 inhibitors group. Moreover, compared with the blank and negative control groups, the apoptosis rates of Treg/CD4+T/CD8+T cells were decreased in the EBI3 mimics group, but the EBI3 inhibitors group exhibited an increase in apoptosis rate. In conclusion, over-expression of EBI3 could reduce the apoptosis of Treg/CD4+T/CD8+T cells and prevent radiation-induced immunosuppression of cervical cancer HeLa cells by inhibiting the activation of PD-1/PD-L1 signaling pathway.


Unusual occurrence of cocoons in population of Haplodiplosis marginata (Diptera: Cecidomyiidae) in Belgium.
The saddle gall midge, Haplodiplosis marginata (von Roser) (Diptera: Cecidomyiidae), is a phytophagous species that develops in saddle-shaped galls on stems of wheat Triticum vulgare, barley Hordeum sativum, rye Secale cereale, and some other species of Poaceae. Only one generation develops per year. Full-grown larvae leave galls and drop onto the soil where they remain up to the springtime of the following year. Larvae do not usually spin cocoons. However, formation of cocoons by larvae was observed in populations developing in western Europe: in England in 1954, in the Netherlands in the 1960s, and in Belgium in 2011. On the basis of our analysis, a part of the larval population forms cocoons as protection against unfavorable weather conditions, especially drought.


Expression of p63 in reactive hyperplasias and malignant lymphomas.
p63 is a recently described p53 homologue. It is involved in survival and differentiation of reserve/stem cells in epithelia. To obtain new insights into the role of p63 in malignant lymphomas (MLs), immunohistochemical staining for p63 and p53 was performed in 126 cases of MLs. p63 was expressed in 38 cases of MLs (30.2%) including 32/61 cases (52.5%) of diffuse large B-cell lymphoma (DLBCL), 1/8 cases (12.5%) of precursor T-lymphoblastic lymphoma (T-LBL), 4/14 cases (28.6%) of follicular lymphoma, 1/6 cases (16.7%) of T/NK cell lymphoma. Among p63 positive cases, p63 was strongly expressed in 15/32 cases of DLBCL and 1/1 case of T-LBL. p63 was not expressed in mantle cell lymphomas, peripheral T-cell lymphomas, marginal zone B-cell lymphomas, plasma cell myelomas and Hodgkin's lymphomas. p63 was coexpressed with p53 in 18/38 p63 positive cases in which only 4 cases were strongly coexpressed. All p63+/p53+ cases were DLBCL. p63 overexpression (above 30%) cases showed significant poor survival (p=0.0228) in DLBCL. However, there was no statistically significant correlation between p63 expression and IPI score on Multivariate analysis. We could speculate that p63 could act indirectly as an oncogene by inhibiting p53 functions. Stage of differentiation of neoplastic lymphocytes appears to have a correlation with p63 expression in MLs.


Brachial Plexus Block for Cancer-Related Pain: A Case Series.
Neoplastic brachial plexopathy (NBP) is caused by a cancerous infiltration into the brachial plexus, presenting often as severe pain in the affected upper extremity. Such pain can be resistant to medical treatment. Invasive interventions such as brachial plexus neurolysis with phenol or cordotomy may result in severe complications including permanent neurological damage and death. Continuous brachial plexus and paravertebral block with local anesthetic have been reported to successfully control pain from NBP, but these techniques are logistically challenging and frequently have catheter-related complications. We report a series of patients who received single-shot brachial plexus blocks with a mixture of local anesthetic and corticosteroid (bupivacaine 0.25% with methyl-prednisolone 20-120 mg) for the treatment of refractory cancer-related pain in the brachial plexus territory, mostly from NBP. Theoretically, such blocks could provide immediate analgesia from the local anesthetic and a longer-lasting analgesia from the slow-release steroids. Responders reported a sustained decrease in their pain (lasting from 2 weeks to 10 months), a significant decrease in their opioid and non-opioid (ketamine, gabapentin) consumption, overall satisfaction with the block, and unchanged or improved function of their limb. The ideal candidate for this procedure is a patient who has pain that is predominantly neuropathic from a lesion within the brachial plexus and with anatomy amenable to ultrasound-guided nerve block. Our case series suggests that, in the appropriately selected patient, this technique can safely and effectively alleviate pain from NBP. The procedure is simple, spares limb function, and can be diagnostic, predicting response to more complex procedures. To the best of our knowledge, this is the first report using this technique for NBP.


Molecular cloning and characterization of a novel putative STE20-like kinase in guinea pigs.
Protein kinases play a key role in cell growth and differentiation. We have isolated the cDNA of a novel protein serine/threonine kinase (referred to as STE20-like kinase (SLK) from a guinea pig liver cDNA library with a probe generated by a cloning approach based on the polymerase chain reaction. The encoded polypeptide (1231 amino acids, M(r) 141,079) contains all conserved subdomains characteristic of the protein serine threonine kinase family. A hemagglutinin-tagged SLK expressed artificially in COS7 cells was hyperphosphorylated by anisomycin. By Northern blot analysis, SLK mRNA was detected in all organs examined: brain, lung heart, liver, kidney, spleen, testis, and eosinophils. Sequence comparisons of its catalytic domain related SLK to p21-activated kinase family of protein serine/threonine kinases. Its noncatalytic domain comprises several intriguing structural features, including the acidic region and the nuclear targeting sequence. This noncatalytic domain exhibited no extended similarity with other proteins. Thus, SLK is a protein serine/threonine kinase which contains an unknown regulatory domain(s).


Clarification of the Identity of the Tea Green Leafhopper Based on Morphological Comparison between Chinese and Japanese Specimens.
Tea green leafhopper is one of the most dominant pests in major tea production regions of East Asia. This species has been variously identified as Empoasca vitis (Goëthe), Jacobiasca formosana (Paoli) and Empoasca onukii Matsuda in Mainland China, Taiwan and Japan, respectively. Recent study of DNA sequence data suggested that treatment of this pest as different species in these three adjacent regions is incorrect and that they were a single species; but the correct scientific name for the species has remained unclear. Consistent with the prior molecular evidence, morphological study shows that the male genital characters of Chinese specimens are the same as those of specimens from Japan, so the correct scientific name of tea green leafhopper in China is Empoasca (Matsumurasca) onukii Matsuda.


Developing a Prototype Pathogen Plan and Research Priorities for the Alphaviruses.
The Togaviridae family, genus, Alphavirus, includes several mosquito-borne human pathogens with the potential to spread to near pandemic proportions. Most of these are zoonotic, with spillover infections of humans and domestic animals, but a few such as chikungunya virus (CHIKV) have the ability to use humans as amplification hosts for transmission in urban settings and explosive outbreaks. Most alphaviruses cause nonspecific acute febrile illness, with pathogenesis sometimes leading to either encephalitis or arthralgic manifestations with severe and chronic morbidity and occasional mortality. The development of countermeasures, especially against CHIKV and Venezuelan equine encephalitis virus that are major threats, has included vaccines and antibody-based therapeutics that are likely to also be successful for rapid responses with other members of the family. However, further work with these prototypes and other alphavirus pathogens should target better understanding of human tropism and pathogenesis, more comprehensive identification of cellular receptors and entry, and better understanding of structural mechanisms of neutralization.


Photoexcited structure of a plant photoreceptor domain reveals a light-driven molecular switch.
The phototropins are flavoprotein kinases that control phototropic bending, light-induced chloroplast movement, and stomatal opening in plants. Two flavin mononucleotide binding light, oxygen, or voltage (LOV) domains are the sites for initial photochemistry in these blue light photoreceptors. We have determined the steady state, photoexcited crystal structure of a flavin-bound LOV domain. The structure reveals a unique photochemical switch in the flavin binding pocket in which the absorption of light drives the formation of a reversible covalent bond between a highly conserved Cys residue and the flavin cofactor. This provides a molecular picture of a cysteinyl-flavin covalent adduct, the presumed signaling species that leads to phototropin kinase activation and subsequent signal transduction. We identify closely related LOV domains in two eubacterial proteins that suggests the light-induced conformational change evident in this structure is an ancient biomolecular response to light, arising before the appearance of plants.


Immunologic thrombocytopenic purpura as presenting symptom of hepatitis C infection.
We report on 3 female patients with immunologic thrombocytopenic purpura (ITP) for whom diagnostic procedures evidenced a chronic Hepatitis C virus (HCV) infection. In 2 cases, a transfusion performed more than 10 years ago represented the probable way of contamination. One patient received a course of steroids, which normalized the platelet counts. Another one has been treated with repeated IV immunoglobulins, which induced partial responses of variable duration. HCV is responsible for many autoimmune manifestations and a search for this virus seems warranted for exploring patients with ITP.


Development of the rat conceptus in vitro and associated changed in components of culture medium.
Rat conceptuses of pregnancy day 11 (embryonic age approximately 10-5 days) with embryos within the yolk and amniotic sacs and polar allantoic placental tissues were cultured by the 'New system' utilizing homologous serum in 60 ml roller bottles with 20% O2, 5% CO2 and 75% N2 gas environment (five conceptuses/10 ml serum). Embryonic growth and development was assessed by external morphology and somite counts, and by measurement of DNA, RNA and protein contents. The embryonic growth was considerably retarded beyond 24 h when culture was extended to 48 h. During continuous culture of conceptuses for 48 h, the partial pressure of O2 in the medium decreased gradually with simultaneous increase of pCO2 and decline of pH values. Glucose level was depleted considerably and small quantities of urea, uric acid and creatinine accumulated in the medium. The concentrations of electrolytes (Na+, K+, Cl-) and total Ca and P, and lactic dehydrogenase activity in the medium increased during the latter part of the 48 h culture period. The growth and differentiation of embryos were significantly improved by transferring conceptuses to fresh serum medium with 40% O2, 5% CO2 and 55% N2 gas phase after 22-24 h culture and continuing the culture for an additional 24 h. Embryos grown in vitro for 48 h developed 39 somites and showed a tenfold increase in DNA content and a five- to seven-fold increase in RNA and protein contents, over initial values.


EGFR tyrosine kinase inhibitor HS-10182 increases radiation sensitivity in non-small cell lung cancers with EGFR T790M mutation.
To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups. Western blot was performed to analyze the expression of phosphorylated EGFR, AKT, DNA-dependent protein kinase, and catalytic subunit (DNA-PKcs) proteins. Immunofluorescence analyses were performed to examine the formation and changes in nuclear γ-H2AX foci. Cell apoptosis was examined by flow cytometry and Western blots for cleaved caspase-3, -8, -9, and cleaved poly ADP-ribose polymerase (PARP). Furthermore, we established xenograft models in mice and the effects of different treatments on tumor growth were then assessed. Clonogenic survival assays revealed that HS-10182 significantly enhanced the radiosensitivity of H1975 cells but not A549 cells [dose enhancement ratios (DERs)=2.36 (P < 0.05) vs. 1.43 (P > 0.05)]. Western blot results showed that HS-10182 increased the levels of cleaved caspase-3, -8, -9, and cleaved PARP in H1975 cells but not in A549 cells. In addition, flow cytometry analysis showed that HS-10182 enhanced irradiation-induced apoptosis in H1975. Immunofluorescence results found that HS-10182 increased the average number of γ-H2AX foci after irradiation in H1975 cells, but not in A549 cells. Combined radiation and HS-10182 treatment increased the expression of DNA-PKcs but this increase was more significant in H1975 cells than in A549 cells. Moreover, HS-10182 suppressed the increased expression of Rad50 in H1975 cells in response to irradiation. In vivo experiments found that the combined therapy significantly inhibited tumor growth. HS-10182 enhances the radiosensitivity of H1975 cells which is possibly because that HS-10182 could enhance irradiation-induced apoptosis, increase irradiation-induced DNA damage, and cause a delay in DNA damage repair. Our findings suggest that radiotherapy combined HS-10182 is a novel treatment for lung cancer cells which have acquired the T790M mutation. HS-10182 could be brought to the clinic as a radiosensitizer in NSCLCs with the EGFR T790M mutation.


Orthodox Christian bioethics.
We cannot ignore the multitude of differences in Christian doctrines. There are more and more divisions and autogenetic beginnings. In talking about religion, we cannot ignore these differences, especially when we are trying to help the seeker. Neither can we ignore these differences when we talk about medical ethics. Care demands that we address both religious and medical issues. We must not, however, attempt to formulate a new religious bioethics in the context of any failure to address the differences and similarities as the record of Christian history reveals. History can reveal to us many things we may not know about ourselves as Christian. Understanding our Christian heritage is essential in order to understand our approach to any Christian bioethic. This essay will look at Christian history to articulate the differences in Orthodox and non-Orthodox formation. Primary focus will be on the Great Schism and the value of natural law theology in the development of Christian bioethics. Reference will be made to end-of-life decision making to clarify the issues.


Growth of nanograins in TiO2 nanofibers synthesized by electrospinning.
Present study focuses the effect of calcination temperature and its duration on the morphology and growth of nanograins in individual TiO2 nanofibers synthesized by electrospinning method. Polyvinyl acetate and titanium tetraisopropoxide were used as chemical precursors along with other standard solvents in the synthesis process. This study shows that synthesized TiO2 nanofibers are randomly arranged and spreads uniformly over the Si substrate and possess polycrystalline nature consisting of nanograins. Similar to the sintering behavior generally observed in bulk ceramics, the nanograins coalesce and grow under higher calcination temperature and longer calcination time. The activation energy for the growth of nanograins is found to be 47.2 kJ/mol. The dominant growth mechanism changes depending on the stages of calcination.


Attributes of occupational injury among workers in the chemical industry and safety issues.
Case-study research was carried out with a view to find the attributes of occupational injury among workers in the chemical industry and to enhance safety issues. Injury data were collected and processed in terms of different variables, such as age, gender, skills, type of hazard, etc. Pareto analysis was then applied to find a pattern of occupational injury among the workers. The study revealed that 79.52% of the injured workers were in the 40-59 age group; 57.14% of accidents occurred during the 1st shift; 73.26% of accidents caused injury to hands, feet, chest to thigh, arms and eyes; and 70.93% of injuries were caused by pumps, carrying and lifting, vehicles, pipelines, valves, and grinding. Surprisingly, no one was injured in the group of temporary workers. The paper also provides specific suggestions followed by some action plans.


[Irradiation of the thyroid gland: changes in its function].
The authors have studied some usual parameters of the evaluation of the thyroid gland function, after secondary irradiation during tele-cobaltherapy treatment in 20 patients with larynx carcinoma. The parameters studied have been iodine uptake, Hamolsky index, T4, FT4 PB127I and cholesterol. The values, statistically treated, enable the conclusion that normal adult thyroid gland has a very low clinical and analytical radiosensibility.


Multiplicity-Selective Coherence Transfer Steps for the Design of Amino Acid-Selective Experiments-A Triple-Resonance Experiment Selective for Asn and Gln
A multiplicity-selective coherence transfer step is discussed, that can replace the normal INEPT transfer in triple-resonance experiments. Depending on the pulse sequence in which they are implemented, amino acid-selective experiments will be created. Two experiments selective for Asn and Gln are proposed. Copyright 1998 Academic Press.


Depth of transference in groups.
An ongoing controversy in the field of group psychotherapy is whether transference regression is greater in groups than in individual treatment. There appears to be a general consensus that group behavior may be understood as operating on at least three levels--the conscious--rational, the oedipally determined transference, and the preoedipal maternal transference level. The more rational levels are associated with transference dilution, whereas the more primitive levels accompany transference intensification. Dilution occurs as a result of reality demands and inputs of the group situation and because of multiple targets of displacement. Transference intensification is a product of mutual stimulation, contagion effect, frustrating inputs, and support of the group theme. Certain patients benefit most from the dilution features of a group, and others profit most from intensification. The therapist's technique and the patient's pathology are the main determinants of which aspect gets emphasized and utilized.


Minimum Corneal Diameter and Anterior Steep Axis Curvature Share the Same Meridian: A Novel Finding.
To define the external scleral sulcus (ESS) on a Scheimpflug image and use it for a morphometric analysis of corneal diameter (CD). Retrospective, cross-sectional study of pediatric Asian-Indian eyes. One random eye of 353 subjects between 5 and 18 years underwent 25-scan Pentacam HR imaging. For all scans, densitometry values along the anterior corneal edge were recorded and differentiated. The peaks on the differentiated curve were chosen as the ESS points, and this distance between them was called CD. Vertical (vCD), maximum (maxCD), minimum (minCD) CD and their meridians were defined. Multiple regression models (MRMs) with CD and other Pentacam parameters were built to predict astigmatism and its axis, mean keratometry (Kmean), and Belin/Ambrósio enhanced ectasia display deviation (BAD-D). MRMs were validated using intraclass correlation coefficient (ICC). Estimated horizontal CD (hCD) was validated against digital caliper measurement using ICC. The ICC (95% CI) between caliper and hCD was 0.96 (0.93, 0.97). MRM predictions (P < .001) used CD parameters, anterior chamber depth, corneal volume and distance from the corneal thinnest location to apex. These predictions achieved an ICC of 0.34 (0.18, 0.46), 0.82 (0.78, 0.86), 0.87 (0.84, 0.89), and 0.81 (0.76, 0.84), respectively. The astigmatism axis prediction depended on the minCD and maxCD meridians. Its within-subject SD (4.97°) was less than 2 consecutive Pentacam scan angles (7.2°). The CD metric strongly correlated with the astigmatism axis, keratometry, and BAD-D. Its spatial description may be significant in corneal treatment planning and disease diagnoses.


Minimally invasive plate osteosynthesis in the treatment of isolated ulnar bone fractures.
Minimally invasive internal fixation is also called "biological internal fixation". This concept is used widely in the treatment of various fractures but to date, there have been no report about such application in the repair of isolated ulnar bone fractures. Eleven patients with fracture of isolated ulnar bone (four AO type 22A11 and seven AO type 22A12), mean age 43.16 (range, 24- 59y), were treated using closed reduction and locking compression plate with minimally invasive plate osteosynthesis (MIPO) with the aim of minimising soft tissue damage. Fractures healed at an average of 7.8 weeks with good to excellent clinical outcomes. There were no complications such as nonunion, implant failure or neurovascular injuries. MIPO seems to be advantageous for soft tissue and bone biology. Good union was seen and fracture complications were also prevented by early mobilisation. Locking compression plate (LCP), closed reduction, isolated ulnar bone fracture, minimally invasive plate osteosynthesis (MIPO).


Growth suppression of cervical carcinoma by pigment epithelium-derived factor via anti-angiogenesis.
Pigment epithelium-derived factor (PEDF), an angiogenesis inhibitor with multiple other functions, balances angiogenesis in the eye and blocks tumor progression. Cervical cancer, an angiogenesis-dependent tumor, is the second most common cancer in women without effective treatment. It has been reported that PEDF can inhibit several types of tumors, however, the potential of PEDF for the treatment of cervical carcinoma has not been well explored. The present study was designed to investigate the effect of recombinant PEDF on the neovascularization and growth of cervical carcinoma. We found for the first time that PEDF was downregulated apparently in human cervical carcinoma nests compared to either normal cervical epithelium or nonneoplastic peritumoral epithelium, suggesting potential anti-angiogenesis function by supplement of PEDF in cervical carcinoma. Intraperitoneal injection of PEDF in xenografted cervical carcinoma mice suppressed tumor growth with 68% reduction. Microvessel density in tumor tissues treated with PEDF was significantly decreased. PEDF dose-dependently inhibited proliferation and induced apoptosis of endothelial cells, but had no direct effect on proliferation and apoptosis of Hela cells under both normoxia and hypoxia. These results suggested that PEDF suppressed tumor growth by blocking angiogenesis instead of a direct cytotoxic effect on tumor cells. VEGF, a major angiogenic stimulator, was downregulated by PEDF in Hela cells by downregulation of HIF-1α, a crucial transcriptional factor for VEGF expression. Downregulation of VEGF expression in tumor cells through inhibiting HIF-1α, thus attenuating the paracrine effect of VEGF on endothelial cells, may represent a mechanism for the anti-angiogenic activity of PEDF.


Improvement in booster seat use in Tennessee.
Tennessee enacted an enhanced child safety restraint law in July 2004, which included new requirements for booster seat use among 4- to 8-year-old children. The goal of this study was to evaluate the appropriate use of child safety restraints and knowledge of the enhanced law before and after its implementation. On-site child safety restraint assessments and brief driver interviews for cars with passengers 0 to 8 years of age were conducted at 34 sites in 3 urban counties in Tennessee. Assessments were conducted 2 to 3 months before implementation of the law and 1 year after implementation of the law. Appropriateness of restraint use was defined on the basis of language in the enhanced law. Data were obtained for 1247 child passengers transported by 1191 drivers; 333 of the children were 0 to 3 years of age, and 914 were 4 to 8 years of age (the primary age group targeted by the enhanced law). Significant improvement in appropriate booster seat use was seen for 4- to 8-year-old passengers after implementation (39%), compared with use before implementation (29%). There was no improvement in the rate of appropriate restraint use for younger children (<4 years of age) after implementation. Black passengers 4 to 8 years of age were twice as likely as white child passengers to be unrestrained, before and after implementation. Seventy-nine percent of drivers reported awareness of the new restraint law after implementation; the majority of drivers obtained information from television advertisements. Improvements in booster seat use were seen after adoption of an enhanced state law requiring use; however, racial differences in restraint use persisted among 4- to 8-year-old passengers. Additional study of barriers to booster seat use among drivers of black child passengers and unrestrained children is warranted.


Physical performance in middle age and old age: good news for our sedentary and aging society.
Physical performance often declines in middle age, but it is unclear to what extent this is due to biological aging. It can be difficult to determine whether such physical changes are truly age-related, as they might alternatively be explained as the negative consequences of a sedentary lifestyle. We assessed the endurance of a physically active subgroup of the population by performing an age- and sex-stratified analysis of over 900,000 running times of marathon and half-marathon participants aged 20 to 79. We also analyzed the responses of 13,171 marathon and half-marathon runners to a questionnaire about sports, lifestyle, and health. No significant age-related decline in performance appears before age 55. Moreover, only a moderate decline is seen thereafter; in fact, 25% of the 65- to 69-year-old runners were faster than 50% of the 20- to 54-year-old runners. Our survey also revealed that more than 25% of the 50- to 69-year-old runners had started their marathon training only in the past 5 years. Performance losses in middle age are mainly due to a sedentary lifestyle, rather than biological aging. The large contingent of older "newcomers" among marathon runners demonstrates that, even at an advanced age, non-athletes can achieve high levels of performance through regular training.


Biological effects of Mammalian translationally controlled tumor protein (TCTP) on cell death, proliferation, and tumorigenesis.
Translationally controlled tumor protein (TCTP) is a highly conserved protein found in eukaryotes, across animal and plant kingdoms and even in yeast. Mammalian TCTP is ubiquitously expressed in various tissues and cell types. TCTP is a multifunctional protein which plays important roles in a number of cell physiological events, such as immune responses, cell proliferation, tumorigenicity, and cell death, including apoptosis. Recent identification of TCTP as an antiapoptotic protein has attracted interest of many researchers in the field. The mechanism of antiapoptotic activity, however, has not been solved completely, and TCTP might inhibit other types of cell death. Cell death (including apoptosis) is closely linked to proliferation and tumorigenesis. In this context, we review recent findings regarding the role of TCTP in cell death, proliferation, and tumorigenesis and discuss the mechanisms.


Sodium movements in the human red blood cell.
Measurements were made of the sodium outflux rate constant, (o)k(Na), and sodium influx rate constant, (i)k(Na), at varying concentrations of extracellular (Na(o)) and intracellular (Na(c)) sodium. (o)k(Na) increases with increasing [Na(o)] in the presence of extracellular potassium (K(o)) and in solutions containing ouabain. In K-free solutions which do not contain ouabain, (o)k(Na) falls as [Na(o)] rises from 0 to 6 mM; above 6 mM, (o)k(Na) increases with increasing [Na(o)]. Part of the Na outflux which occurs in solutions free of Na and K disappears when the cells are starved or when the measurements are made in solutions containing ouabain. As [Na(o)] increases from 0 to 6 mM, (i)k(Na) decreases, suggesting that sites involved in the sodium influx are becoming saturated. As [Na(c)] increases, (o)k(Na) at first increases and then decreases; this relation between (o)k(Na) and [Na(c)] is found when the measurements are made in high Na, high K solutions; high Na, K-free solutions; and in (Na + K)-free solutions. The relation may be the consequence of the requirement that more than one Na ion must react with the transport mechanism at the inner surface of the membrane before transport occurs. Further evidence has been obtained that the ouabain-inhibited Na outflux and Na influx in K-free solutions represent an exchange of Na(c) for Na(o) via the Na-K pump mechanism.


Head-to-Head Comparison of Two Plasma Phospho-tau Assays in Predicting Conversion of Mild Cognitive Impairment to Dementia.
Among blood biomarkers, phospho-tau181 (pTau181) is one of the most efficient in detecting Alzheimer disease across its continuum. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors. Here we tested the Lumipulse assay for plasma pTau181 in mild cognitive impairment (MCI) participants from the Baltazar prospective cohort. We compared the performance of this assay to the corresponding Simoa assay for the prediction of conversion to dementia. We also evaluated the association with various routine blood parameters indicative of comorbidities. Lumipulse and Simoa gave similar results overall, with hazard ratios for conversion to dementia of 3.48 (95% CI, 2.23-5.45) and 3.70 (95%CI, 2.39-5.87), respectively. However, the 2 tests differ somewhat in terms of the patients identified, suggesting that their use may be complementary. When combined with age, sex, and apolipoprotein E (APOE)ε4 status, areas under the curves for conversion detection were 0.736 (95% CI, 0.682-0.791) for Lumipulse and 0.733 (95% CI, 0.679-0.788) for Simoa. Plasma pTau181 was independently associated with renal dysfunction (assessed by creatinine and glomerular filtration) for both assays. Cardiovascular factors (adiponectin and cholesterol), nutritional, and inflammatory markers (total protein content, C-reactive protein) also impacted plasma pTau181 concentration, although more so with the Simoa than with the Lumipulse assay. Plasma pTau181 measured using the fully automated Lumipulse assay performs as well as the Simoa assay for detecting conversion to dementia of MCI patients within 3 years and Lumipulse is less affected by comorbidities. This study suggests a pathway to routine noninvasive in vitro diagnosis-approved testing to contribute to the management of Alzheimer disease. NCT01315639.


[Physiologic and hygienic principles underlying creation of clothes protecting against cold].
The article presents principles underlying creation of clothes protecting against cold, in accordance with specific usage conditions (ambient air temperature and speed, ergonomic traits and metabolic level of work, duration of cold exposure). The authors listed requirements to thermal protection of clothes and to separate entities (hat, gloves, shoes) in relation to various climate regions. Major steps of creation and evaluation of the clothes are demonstrated.


Site Engineering of Covalent Organic Frameworks for Regulating Peroxymonosulfate Activation to Generate Singlet Oxygen with 100 % Selectivity.
Singlet oxygen (1 O2 ) is an excellent reactive oxygen species (ROSs) for the selective conversion of organic matter, especially in advanced oxidation processes (AOPs). However, due to the huge dilemma in synthesizing single-site type catalysts, the control and regulation of 1 O2 generation in AOPs is still challenging and the underlying mechanism remains largely obscure. Here, taking advantage of the well-defined and flexibly tunable sites of covalent organic frameworks (COFs), we report the first achievement in precisely regulating ROSs generation in peroxymonosulfate (PMS)-based AOPs by site engineering of COFs. Remarkably, COFs with bipyridine units (BPY-COFs) facilitate PMS activation via a nonradical pathway with 100 % 1 O2 , whereas biphenyl-based COFs (BPD-COFs) with almost identical structures activate PMS to produce radicals (⋅OH and SO4 .- ). The BPY-COFs/PMS system delivers boosted performance for selective degradation of target pollutants from water, which is ca. 9.4 times that of its BPD-COFs counterpart, surpassing most reported PMS-based AOPs systems. Mechanism analysis indicated that highly electronegative pyridine-N atoms on BPY-COFs provide extra sites to adsorb the terminal H atoms of PMS, resulting in simultaneous adsorption of O and H atoms of PMS on one pyridine ring, which facilitates the cleavage of its S-O bond to generate 1 O2 .


Monodeiodination of thyroxine in the maternal and fetal dog kidneys and placenta.
We studied the monodeiodinating activities of the dog placenta and the pregnant dog kidney and compared them with those of the non-pregnant dog kidney and fetal kidney. Each tissue was homogenized in 50 mM Tris/HC1 buffer, pH 7.5. The homogenate (1 mg protein) was incubated with 1 microgram of T4 at 37 degrees C in the air for 15 min or 60 min in the presence of 5 mM DTT. The T3 and reverse T3 generated in the reaction mixture were extracted into cold ethanol and then measured by RIA. Sulfhydryl group content in each tissue was determined. The characteristics of monodeiodinating activity of the dog placenta were in good concordance with those of the rat and human placentas. Net reverse T3 production in the dog placenta was 1.4-13.2 (6.1 +/- 5.3, mean +/- S.D.) ng/mg protein/micrograms T4/60 min but net T3 production was negligible. Although it seemed that the T3 production/reverse T3 production ratio in the pregnant dog kidney was lower than that in the non-pregnant dog kidney, there was no statistical significance. It is conceivable that the characteristics of deiodination in the placenta are tissue specific, independent of the changes in internal conditions induced by pregnancy. In the fetal dog kidney homogenate, T3 and reverse T3 were metabolized only minimally and productions of T3 and reverse T3 were also very low. An increase in DTT concentration up to 100 mM had no effect on the production rates of these triiodothyronines . Total and non-protein SH group contents in the fetal dog kidney homogenate were about the half of those in the maternal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Teledentistry awareness, its usefulness, and challenges among dental professionals in Pakistan and Saudi Arabia.
This study aims to describe the perception of dental professionals in Pakistan and Saudi Arabia (SA) towards the practice of teledentistry, its usefulness and challenges. A cross-sectional study was carried out among 190 dentists from January 2021 to April 2021. The participants were included in the study using snowball sampling method. A 26-item adopted questionnaire was distributed using different social media channels. Chi-square test was used for analysis. Out of 190 participants, 46.3% were from Pakistan and 53.7% were from SA. The majority of participants in both countries agreed that teledentistry would enhance guidelines and advice (74.2%), improve peer-to-peer interaction (79.5%) and make patient's referrals more efficient (75.8%). For the usefulness, most participants agree that it is economical for the patients (61.1%), improves communication (74.7%), helps in educating the patients (86.3%), avoid unnecessary travel (76.8%), helps monitoring (71.6%), and benefits patients in remote areas (74.7%); however, more Pakistani participants perceived that time spent with the patient would increase compared to SA participants (p < 0.001) and a higher proportion of SA participants believe that it helps in communication and monitoring of patients (p < 0.001) than Pakistani participants. Regarding the challenges in the use of teledentistry, few participants think that it violates the patient's privacy (22.6%) or is difficult to use (14.7%) or have distrust towards the teledentistry equipment (24.2%). The results indicated a high awareness and a positive attitude towards teledentistry, and its adaptation in their dental practice in both countries. However, limited infrastructure, set-up cost, and information technology (IT) literacy are the main challenges in integrating teledentistry which can be overcome by strategic government initiatives, policies, and programs.


Ozonation of Para-Substituted Phenolic Compounds Yields p-Benzoquinones, Other Cyclic α,β-Unsaturated Ketones, and Substituted Catechols.
Phenolic moieties are common functional groups in organic micropollutants and in dissolved organic matter, and are exposed to ozone during drinking water and wastewater ozonation. Although unsubstituted phenol is known to yield potentially genotoxic p-benzoquinone during ozonation, little is known about the effects of substitution of the phenol ring on transformation product formation. With batch experiments employing differing ozone/target compound ratios, it is shown that para-substituted phenols ( p-alkyl, p-halo, p-cyano, p-methoxy, p-formyl, p-carboxy) yield p-benzoquinones, p-substituted catechols, and 4-hydroxy-4-alkyl-cyclohexadien-1-ones as common ozonation products. Only in a few cases did para-substitution prevent the formation of these potentially harmful products. Quantum chemical calculations showed that different reaction mechanisms lead to p-benzoquinone, and that cyclohexadienone can be expected to form if no such pathway is possible. These products can thus be expected from most phenolic moieties. Kinetic considerations showed that substitution of the phenolic ring results in rather small changes of the apparent second order rate constants for phenol-ozone reactions at pH 7. Thus, in mixtures, most phenolic structures can be expected to react with ozone. However, redox cross-reactions between different transformation products, as well as hydrolysis, can be expected to further alter product distributions under realistic treatment scenarios.


The epidemiology of human rotavirus associated with diarrhoea in Kenyan children: a review.
Rotavirus gastroenteritis still remains a major cause of morbidity and mortality among young children in developing countries, with approximately 150,000-200,000 deaths occurring annually in sub-Saharan Africa. We reviewed papers published over the last 30 years on the epidemiology of rotavirus diarrhoea among the hospitalized and out-patient children in Kenya. The analysis shows rotavirus prevalence of 6-56% with diarrhoea occurring throughout the year and generally exhibiting distinct peaks during the dry months. Among the common genotype, G1 was the most predominant up to the year 2002 but more recently there has been an emergence of genotype G9 as the most predominant genotype and to a less extent G8. It is important to continue rotavirus surveillance in Kenya to determine accurately the burden of rotavirus disease and the emerging new genotypes. This will assist policy makers in decision making on rotavirus vaccine introduction and determining the impact of the vaccine.


The interaction of housing condition and acute immobilization stress on the elevated plus-maze behaviors of protein-malnourished rats.
Protein malnutrition induces structural, neurochemical and functional alterations in the central nervous system, leading to behavioral alterations. In the present study, we used the elevated plus-maze (EPM) as a measure of anxiety to evaluate the interaction between acute immobilization and housing conditions on the behavior of malnourished rats. Pups (6 males and 2 females) were fed by Wistar lactating dams receiving a 6% (undernourished) or 16% (well-nourished) protein diet. After weaning, the animals continued to receive the same diets ad libitum until 49 days of age when they started to receive a regular lab chow diet. From weaning to the end of the tests on day 70, the animals were housed under two different conditions, i.e., individual or in groups of three. On the 69th day, half of the animals were submitted to immobilization for 2 h, while the other half were undisturbed, and both groups were tested 24 h later for 5 min in the EPM. Independent of other factors, protein malnutrition increased, while immobilization and social isolation per se decreased, EPM exploration. Analysis of the interaction of diet vs immobilization vs housing conditions showed that the increased EPM exploration presented by the malnourished group was reversed by acute immobilization in animals reared in groups but not in animals reared individually. The interaction between immobilization and housing conditions suggests that living for a long time in social isolation is sufficiently stressful to reduce the responses to another anxiogenic procedure (immobilization), while living in groups prompts the animals to react to acute stress. Thus, it is suggested that housing condition can modulate the effects of an anxiogenic procedure on behavioral responses of malnourished rats in the EPM.


MiR-139-5p inhibits proliferation and promoted apoptosis of human airway smooth muscle cells by downregulating the Brg1 gene.
MicroRNAs have emerged as critical regulators in the pathogenesis of asthma. However, the role of microRNAs in asthma needs to be further elucidated. In this study, we found that miR-139-5p was greatly decreased in airway smooth muscle (ASM) cells from asthmatic humans as well as ASM cells stimulated with cytokines. Overexpression of miR-139-5p markedly suppressed ASM cell proliferation and promoted cell apoptosis, whereas knockdown of miR-139-5p had the opposite effect. Further study verified that Brg1, a chromatin remodeling factor, was upregulated in ASM cells treated with cytokines and acted as a direct target of miR-139-5p. Ectopic expression of Brg1 partially reversed the effect of miR-139-5p on cell proliferation and apoptosis. Moreover, overexpression of Brg1 restored miR-139-5p-induced downregulation of Akt and p70S6K phosphorylation. Together, these data indicate that miR-139-5p may function as a key regulator of ASM cell proliferation and apoptosis, potentially by targeting the Brg1 gene, and thus suggesting a potential role of miR-139-5p in the pathogenesis of asthma.


Platinum nanopeapods: spatial control of mesopore arrangements by utilizing a physically confined space.
Spherical mesopores: Mesoporous Pt rods containing cage-type mesopores were prepared with porous anodic alumina membranes (PAAMs). It is noteworthy that spherical mesopores are aligned in the rods due to physical confinement by the PAAM channels. Both the mesopore alignment and the morphological control are realized simultaneously, which could be important for bottom-up approaches to nanometals with desirable structural features (see figure).


Control of Structural Coloration by Natural Sunlight Irradiation on a Melanin Precursor Polymer Inspired by Skin Tanning.
Natural melanin affects the reflection and absorption of light, and it is known as an important element in producing bright structural colors in nature. In this study, we prepared core-shell particles using a melanin precursor polymer, that is, polytyrosine (PTy), as a shell layer by the oxidative polymerization of tyrosine ethyl ester (Ty) in the presence of cerium oxide (CeO2) core particles. Inspired by skin tanning, irradiating the CeO2@PTy core-shell particles with UV or natural sunlight caused melanization by extending the π-conjugated length of PTy, producing colloidal particles with the ability to absorb light. The pellet samples consisting of CeO2@PTy particles appeared whitish because of multiple scattered light. In contrast, the light absorption capacity of CeO2@PTy UV or CeO2@PTy Sun particles after light irradiation suppressed scattered light, dramatically improving the visibility of the structural color of the pellet samples made from these particles. Thus, a new method has been developed to control the visualization of structural colors to the human eye by irradiating the melanin precursor polymer with light.


Effect of a Training Strategy in Improving Medication Fallacies During Pediatric Cardiopulmonary Resuscitation: A Before-and-After Study From a Developing Country.
This study aims to evaluate the effect of structured training on resident performance in improving medication fallacies during pediatric cardiopulmonary resuscitation (CPR). This before-and-after study was conducted in the pediatric acute care areas of tertiary care teaching hospitals of a developing country from August to December 2015. Case records of children younger than 18 years who underwent CPR were reviewed. Senior residents rotating through pediatric emergency department and pediatric intensive care unit were evaluated for their knowledge. Incidence of medication fallacies in pediatric CPR and change in the knowledge scores of residents posted in these areas were the main outcome measures. One-hundred records were evaluated (pre-intervention, 54; post-intervention, 46). In the pre-intervention period, 25 had medication fallacies (documentation, 16; dosing, 9). In the post-intervention period, 7 fallacies pertaining to documentation (not dosing) were found. The incidence of severe fallacies decreased from 20% pretraining to 0% posttraining. The mean (SD) knowledge scores of residents increased from 7.9 (2.9) pretraining to 13 (1.4) posttraining. On univariate analysis, fallacies were found to be less if the resident was formally trained (pediatric advanced life support certified), if the patient was older, and during morning and night shifts as compared with evening shift. On multivariate analysis, however, only status of training (posttraining) (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.68) and the morning shift (adjusted odds ratio, 0.03; 95% confidence interval, 0.001-0.72) remained significant with lower incidence of fallacies associated with these variables. Rates of medication fallacies in pediatric CPR declined with structured training. Documentation fallacies may not be eliminated completely with only 1-time training.


Transcriptional activity of the neuron-specific enolase (NSE) promoter in murine embryonic stem (ES) cells and preimplantation embryos.
Mouse embryonic stem (ES) cells were transfected with a plasmid composed of an E. coli lacZ gene fused to 1.8 kb of rat neuron-specific enolase (NSE) promoter sequences. While this reporter construct had been shown previously to function exclusively in postmitotic neurons and neuro-endocrine cells of transgenic mice, stably transfected ES cell clones unexpectedly displayed beta-galactosidase (beta-Gal) activity in the undifferentiated state. This transcriptional activity of the heterologous NSE promoter was confirmed by the identification of endogenous NSE mRNA in undifferentiated ES cells, mouse morulae and blastocysts. NSE protein, however, could not be found in undifferentiated ES cells. Interestingly, in ES cells which were cultured for 7 days under differentiation conditions in vitro, beta-Gal activity decreased to basal levels consistent with the parallel down-regulation of endogenous NSE mRNA. In contrast, prolonged culture of ES cells under differentiation conditions led to the reappearance of NSE mRNA and beta-Gal activity after 17 days. Significant increases in beta-Gal activity were also observed in ES cells which were cultured either on dishes coated with attachment factors such as laminin and gelatin or in the presence of nerve growth factor (NGF). These results suggest that i) transcriptional control mechanisms regulating neuronal gene expression are present at early developmental stages in the mouse and ii) ES cells provide a useful in vitro model system for the analysis of developmentally regulated cellular and molecular events coupled to neuron-specific enolase promoter activity.


Cerebral Reorganization in Subacute Stroke Survivors after Virtual Reality-Based Training: A Preliminary Study.
Functional magnetic resonance imaging (fMRI) is a promising method for quantifying brain recovery and investigating the intervention-induced changes in corticomotor excitability after stroke. This study aimed to evaluate cortical reorganization subsequent to virtual reality-enhanced treadmill (VRET) training in subacute stroke survivors. Eight participants with ischemic stroke underwent VRET for 5 sections per week and for 3 weeks. fMRI was conducted to quantify the activity of selected brain regions when the subject performed ankle dorsiflexion. Gait speed and clinical scales were also measured before and after intervention. Increased activation in the primary sensorimotor cortex of the lesioned hemisphere and supplementary motor areas of both sides for the paretic foot (p < 0.01) was observed postintervention. Statistically significant improvements were observed in gait velocity (p < 0.05). The change in voxel counts in the primary sensorimotor cortex of the lesioned hemisphere is significantly correlated with improvement of 10 m walk time after VRET (r = -0.719). We observed improved walking and increased activation in cortical regions of stroke survivors after VRET training. Moreover, the cortical recruitment was associated with better walking function. Our study suggests that cortical networks could be a site of plasticity, and their recruitment may be one mechanism of training-induced recovery of gait function in stroke. This trial is registered with ChiCTR-IOC-15006064.


Kounis syndrome following multiple wasp stings: A case report.
This is a case of Kounis syndrome with chest tightness, lightheadedness, unconsciousness, and features of shock following multiple wasp stings. Despite cardiopulmonary resuscitation and management of allergic and cardiac symptoms, the patient died. Kounis syndrome should be suspected when a patient presents with allergic symptoms and acute coronary syndrome.


Genetic diversity of the Mycobacterium tuberculosis Beijing family in East Asia revealed through refined population structure analysis.
The Beijing/W family is the endemic lineage of Mycobacterium tuberculosis in East Asia: it has disseminated worldwide. To elucidate its genetic diversity in Japan, phylogenetic reconstruction was performed using 403 M. tuberculosis Beijing family clinical isolates. Variable number of tandem repeats analysis revealed the strains from Japan to be dispersed mainly among five subgroups in a phylogenetic tree. Interestingly, the genotypes of the strains from China and Mongolia were restricted mainly to a single branch; they exhibited high clonality. IS6110 insertion in the NTF region was also analyzed. The majority (78.6%) of Japanese isolates belonged to the ancient sublineage. The modern Beijing strains were observed to correspond to the branch containing the foreign strains, although the ancient Beijing strains were dispersed among the tree's other branches. Our results reflect the singular genetic diversity and the epidemiological pattern of Beijing M. tuberculosis in Japan.


Assessing collaboration among team scientists within a triadic research center partnership.
Few studies have utilized qualitative methods to assess the perceived effectiveness of collaboration among research center interdisciplinary team scientists. Stages of team development served as the theoretical framework to characterize minority serving institution (MSI) and predominantly White institutions (PWI) participants' challenges and successes during a National Institutes of Health (NIH) sponsored cancer health disparities training and research program. We present the finding of an inductive analysis of four open-ended survey questions across two years. Fostering an awareness of the inherently taxing, yet centrality of group (team) development may advance an understanding of team dynamics and lead to increased team cohesion and productivity. In conclusion, we provide recommendations to assist multiple principal investigators who embark on team development.


Conventional and Complementary Healthcare Utilization Among US Adults With Cardiovascular Disease or Cardiovascular Risk Factors: A Nationally Representative Survey.
Background Cardiovascular diseases (CVDs) and their risk factors need guideline-oriented treatment to provide the best benefit for patients. These guidelines include recommendations for regular checkups, realized by general medical practitioners. In addition, individuals with CVD or CVD risk factors tend to use complementary methods for their condition. There is limited information on the association between complementary healthcare utilization and the adherence to recommended conventional health care. Methods and Results In this cross-sectional analysis of the nationally representative 2017 National Health Interview Survey (n=26 742; response rate 80.7%) we examined the prevalence of conventional and complementary healthcare utilization within the past 12 months in individuals with CVD and/or CVD risk factors and the interactions between the two categories of health care. Of all participants, 38.1% reported risk factors for CVD and 11.4% a CVD diagnosis (groups show an overlap). Overall prevalence of visits to conventional and complementary medicine providers and the use of mind-body medicine was high within the population analyzed. Individuals with CVD and/or CVD risk factors using complementary health care were as likely or more likely to consult general practitioners (CVD: adjusted odds ratio [aOR], 1.17; 95% CI, 0.93-1.47; CVD risk: aOR, 1.21; 95% CI, 1.05-1.39) and medical specialists (CVD: aOR, 1.38; 95% CI, 1.17-1.64; CVD risk: aOR, 1.42; 95% CI, 1.28-1.58) than those not using complementary health care. Those using complementary health care were as likely to adhere to medical checkup as those not using complementary health care. Conclusions Complementary healthcare utilization use was not associated with a reduced adherence to conventional health care and recommended checkups. The potential positive association of complementary and conventional healthcare utilization needs to be confirmed in further studies.


[Ultrasound of the bladder neck-urethra transition before and after pelvic floor training with Kolpexin].
In this study we examined sonographically the position of the bladder neck in healthy control persons and patients suffering from stress incontinence before and after pelvic floor exercises supported by Kolpexin. 14 of the 20 patients are satisfied after performing the Kolpexin exercises. We found by using perineal sonography a significant decrease of the angle gamma after the pelvic floor training. The perineal sonography allows good informations about the position of the bladder neck after conservative treatment, too.


Flow cytometry as a quantitative and sensitive method to evaluate low dose radiation induced apoptosis in vitro in human peripheral blood lymphocytes.
Human peripheral blood lymphocytes, irradiated in vitro, die by an apoptotic process. The number of apoptotic cells after in vitro gamma-irradiation (0, 0.1, 0.2, 1, 2 and 5 Gy) was measured by flow cytometry using Annexin V and DiOC6 (a cationic dye) after 24 and 48 h incubation. The mean dose-response curves for apoptosis of six healthy volunteers obtained with both methods were steep below 1 Gy and flatter at higher doses. A slightly higher number of apoptotic cells was observed with DiOC6, compared to Annexin V. This can be assigned to a minor DiOC6-int/PI- population. Forty-eight hour cultures contained higher numbers of apoptotic cells compared with 24 h cultures. For both culture times, DiOC6 and Annexin V detected a statistically significant difference between a control sample and a 0.1 Gy irradiated one, illustrating the high sensitivity of the methods.


Atomic visualization of flipped-back conformations of high mannose glycans interacting with cargo lectins: An MD simulation perspective.
Protein-carbohydrate interactions play a crucial role in mediating several biomolecular recognition events. We attempt to unravel its intricacies by understanding how carbohydrate-binding proteins interpret the glycan code. We aim to decipher lectin-mediated recognition in the endoplasmic reticulum (ER), which plays a crucial role in ER-mediated quality control (ER-QC). The ER-QC functions in three phases-protein folding, transport, and degradation. Altered protein QC leads to ER-related storage disorders. Cargo transport proteins-Ergic53 and Vip36-necessary for maintaining cellular homeostasis-are our primary focus. They recognize monoglucosylated/high mannose N-glycans on the folded glycoproteins. This article reports on the first dynamic investigation of the ER cargo lectins in complex with the high mannose glycans using an advanced sampling technique-replica exchange molecular dynamics to decipher the inherent conformational heterogeneity and the binding mechanism. The study involves simulations for the proteins complexed with three high mannose glycans-Man8B, Man9, and mono-glucosylated glycan. The recognition process is captured using MD simulations to achieve mechanistic insights and characterize the dynamics of glycans in their native and bound states via dihedral angle analysis. Results indicate that the flipped conformation of the glycans was crucial in differentiating their interaction with the proteins. Similar conformers of the glycans are preferred for Ergic53 and Vip36 in their glycan recognition events. Ergic53 preferred Man8B while it was Man9 for Vip36, in coherence with the previous experimental reports. These simulations provide a computational microscopic purview of the mechanism at both spatial and temporal scales. The results correlate with the published experimental data on the specificities of these lectins.


Undersampling artifact reduction for free-breathing 3D stack-of-radial MRI based on a deep adversarial learning network.
Stack-of-radial MRI allows free-breathing abdominal scans, however, it requires relatively long acquisition time. Undersampling reduces scan time but can cause streaking artifacts and degrade image quality. This study developed deep learning networks with adversarial loss and evaluated the performance of reducing streaking artifacts and preserving perceptual image sharpness. A 3D generative adversarial network (GAN) was developed for reducing streaking artifacts in stack-of-radial abdominal scans. Training and validation datasets were self-gated to 5 respiratory states to reduce motion artifacts and to effectively augment the data. The network used a combination of three loss functions to constrain the anatomy and preserve image quality: adversarial loss, mean-squared-error loss and structural similarity index loss. The performance of the network was investigated for 3-5 times undersampled data from 2 institutions. The performance of the GAN for 5 times accelerated images was compared with a 3D U-Net and evaluated using quantitative NMSE, SSIM and region of interest (ROI) measurements as well as qualitative scores of radiologists. The 3D GAN showed similar NMSE (0.0657 vs. 0.0559, p = 0.5217) and significantly higher SSIM (0.841 vs. 0.798, p < 0.0001) compared to U-Net. ROI analysis showed GAN removed streaks in both the background air and the tissue and was not significantly different from the reference mean and variations. Radiologists' scores showed GAN had a significant improvement of 1.6 point (p = 0.004) on a 4-point scale in streaking score while no significant difference in sharpness score compared to the input. 3D GAN removes streaking artifacts and preserves perceptual image details.


Standard microlithographic mosaics to assess endothelial cell counting methods by light microscopy in eye banks using organ culture.
To develop standard microscopic hexagonal mosaics mimicking the human corneal endothelium for quality control of endothelial cell density (ECD) measurement and verification of cell counting strategy by light microscopy in eye banks using organ culture. A standard slide, the Keratotest, was developed with 10 laser-engraved mosaics and different predetermined "cell" densities representing the range of ECDs observed routinely. Horizontal and vertical micrometric scales were etched adjacently to each mosaic, and a standard microscopy resolution test pattern was included. The Keratotest was applied to assess the reliability of a computer-assisted analyzer developed for corneal endothelial evaluation based on light microscopy images. The Keratotest consisted of 10 microlithographic homogeneous mosaics of 1-mm2 printed area and 1.2-microm cell boundary thickness. The micrometric scale associated with each mosaic aided in simultaneous verification of microscope calibration, and the test pattern aided in checking the microscope resolution. The design was unalterable and reproducible, and the glass slide incorporated in a carbon fiber support ensured easy handling and safe transport. Evaluation of the Keratotest mosaics by the computer-assisted analyzer found a high level of agreement (error margin between +0.12 and -0.46%) with the laser-engraved cell density. This prototype device enabled assessment of reliability of ECD measurement in eye banks. It also allowed verification of the calibration and resolution of light microscopes. Periodic validation of counting procedure in eye banks with mosaics of known "cell" densities should be useful for standardization of donor corneal tissue quality control.


Methicillin-resistant Staphylococcus aureus bacteriuria.
Methicillin-resistant Staphylococcus aureus (MRSA) bacteriuria was detected in 11 of 41 patients colonized or infected with MRSA. The patients with bacteriuria generally were older than 40 years of age, five were diabetic, seven had prior indwelling uretheral catheters, two had undergone other urologic manipulations, and only one was clinically symptomatic. Eight patients received variable combinations of antibiotic therapy prior to the diagnosis of MRSA bacteriuria, and seven were still on antibiotic therapy at the time the bacteriuria was detected. Bacteriuria lasted four days to 14 weeks, and was eradicated promptly with cephalosporin therapy in five six patients. Bacteriuria in the untreated patients cleared spontaneously in one month. A single MRSA serotype (83A) predominated. The MRSA isolates were resistant in vitro to most antibiotics except vancomycin. Resistant colonies were observed within cephalothin disc zones of inhibition at 30C (resistance was confirmed by microtube-dilution sensitivity testing). MRSA disc sensitivity testing for cephalothin may be unreliable when performed at 35C.


Protective effect of melatonin against fractionated irradiation-induced epiphyseal injury in a weanling rat model.
The effects of melatonin, a free-radical scavenger and a general antioxidant, on radiation-induced growth plate injury have not been studied previously. The purpose of this study was to determine the potential benefits of sparing longitudinal bone growth by fractionated radiotherapy alone compared with pretreatment with melatonin that provides differential radioprotection of normal cells. Weanling 4-wk-old (75-100 g) male Sprague-Dawley rats were randomly assigned to one of three groups: Group R received fractionated radiation alone (n = 8); groups M5 (n = 8) and M15 (n = 7) received 5 or 15 mg/kg melatonin prior to fractionated radiation, respectively. The distal femur and proximal tibia in the right leg of each animal were exposed to a therapeutic X-irradiation dose (25 Gy total in three fractions) with the contralateral left leg as the non-irradiated control. Melatonin was administered intraperitoneally to the animals 30 min before radiation exposure. Six weeks after treatment, the rats were killed and the lower limbs disarticulated, skeletonized, radiographed, and bone growth was calculated based on measurement of the bone lengths. Fractionated radiation resulted in a mean percent overall limb growth loss of 41.2 +/- 9.5 and a mean percent overall limb discrepancy of 11.2 +/- 2.2. The administration of 5 or 15 mg/kg melatonin before each of the three fractions of radiotherapy reduced the mean percent overall limb growth loss to 33.9 +/- 5.8 and 32.2 +/- 4.5, respectively, and the mean percent overall limb discrepancy to 9.4 +/- 1.6 and 8.9 +/- 1.1, respectively; these values were significantly different compared with irradiation alone (range: P = 0.01-0.04). When compared with Group R, the growth arrest recovered by 5 or 15 mg/kg melatonin was 19.7 and 24.1% for the tibia, 7 and 18.6% for the femur, and 17.7 and 21.8% for the total limb, respectively. These results support further investigation of melatonin in combination with fractionation for potential use in growing children requiring radiotherapy to the extremity for malignant tumors.


Environmental risk factors of leptospirosis in urban settings: a systematic review protocol.
Leptospirosis is the most common zoonotic disease that causes morbidity and mortality worldwide. The disease can cause sporadic epidemics and recent epidemics have become more apparent in urban localities. There is lack of documented evidence on the specific risk factors of leptospirosis infection among the urbanites, thereby impeding initiatives for prevention in urban settings. We aim to systematically search published articles and synthesise evidence on the risk factors associated with leptospirosis infection among the susceptible populations in urban localities, particularly to identify the risk factors of non-recreational leptospirosis infection. We will conduct a systematic review of observational studies that investigated environmental risk factors of leptospirosis in urban localities. The search will be performed for any eligible articles from selected electronic databases from 1970 until May 2018. The study will include any studies that investigated risk factors of confirmed leptospirosis cases who acquired the infection in urban locality, particularly exposures from the non-recreational and non-water-related activities. Study selection and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guideline. All data will be extracted using a standardised data extraction form and quality of the studies will be assessed using the Newcastle-Ottawa Scale guideline. Descriptive and meta-analysis will be performed by calculating the standardised median ORs and risk ratios for types of the non-recreational risk factors stratified by social, living conditions and environmental exposures, types of reservoirs and transmissions and types of activities and employments associated with leptospirosis infection in urban locality. No primary data will be collected thus no formal ethical approval is required. The results will be disseminated though a peer-reviewed publication and conference presentation. CRD42018090820.


Modified lateral orbitotomy for intact removal of orbital dumbbell dermoid cyst.
: We describe a modified lateral orbitotomy for intact removal of a dumbbell dermoid cyst involving the frontozygomatic suture. The clinical features and surgical treatment of the case are discussed.


Lethal coinfection of influenza virus and Streptococcus pneumoniae lowers antibody response to influenza virus in lung and reduces numbers of germinal center B cells, T follicular helper cells, and plasma cells in mediastinal lymph Node.
Secondary Streptococcus pneumoniae infection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. In the lung, lethal coinfection significantly increased virus titers and bacterial cell counts and decreased the level of virus-specific IgG, IgM, and IgA, as well as the number of B cells, CD4 T cells, and plasma cells. Lethal coinfection significantly reduced the size and weight of spleen, as well as the number of B cells along the follicular developmental lineage. In mediastinal lymph nodes, lethal coinfection significantly decreased germinal center B cells, T follicular helper cells, and plasma cells. Adoptive transfer of influenza virus-specific immune serum to coinfected mice improved survival, suggesting the protective functions of anti-influenza virus antibodies. In conclusion, coinfection reduced the B cell response to influenza virus. This study helps us to understand the modulation of the B cell response to influenza virus during a lethal coinfection. Secondary pneumococcal infection after influenza virus infection is an important clinical issue that often results in excess mortality. Since antibodies are key mediators of protection, this study aims to examine the antibody response to influenza virus and demonstrates that lethal coinfection reduced the B cell response to influenza virus. This study helps to highlight the complexity of the modulation of the B cell response in the context of coinfection.


Multi-dimensional machine learning approaches for fruit shape phenotyping in strawberry.
Shape is a critical element of the visual appeal of strawberry fruit and is influenced by both genetic and non-genetic determinants. Current fruit phenotyping approaches for external characteristics in strawberry often rely on the human eye to make categorical assessments. However, fruit shape is an inherently multi-dimensional, continuously variable trait and not adequately described by a single categorical or quantitative feature. Morphometric approaches enable the study of complex, multi-dimensional forms but are often abstract and difficult to interpret. In this study, we developed a mathematical approach for transforming fruit shape classifications from digital images onto an ordinal scale called the Principal Progression of k Clusters (PPKC). We use these human-recognizable shape categories to select quantitative features extracted from multiple morphometric analyses that are best fit for genetic dissection and analysis. We transformed images of strawberry fruit into human-recognizable categories using unsupervised machine learning, discovered 4 principal shape categories, and inferred progression using PPKC. We extracted 68 quantitative features from digital images of strawberries using a suite of morphometric analyses and multivariate statistical approaches. These analyses defined informative feature sets that effectively captured quantitative differences between shape classes. Classification accuracy ranged from 68% to 99% for the newly created phenotypic variables for describing a shape. Our results demonstrated that strawberry fruit shapes could be robustly quantified, accurately classified, and empirically ordered using image analyses, machine learning, and PPKC. We generated a dictionary of quantitative traits for studying and predicting shape classes and identifying genetic factors underlying phenotypic variability for fruit shape in strawberry. The methods and approaches that we applied in strawberry should apply to other fruits, vegetables, and specialty crops.


Past and Current Perspectives in Modeling Bacteria and Blood-Brain Barrier Interactions.
The central nervous system (CNS) barriers are highly specialized cellular barriers that promote brain homeostasis while restricting pathogen and toxin entry. The primary cellular constituent regulating pathogen entry in most of these brain barriers is the brain endothelial cell (BEC) that exhibits properties that allow for tight regulation of CNS entry. Bacterial meningoencephalitis is a serious infection of the CNS and occurs when bacteria can cross specialized brain barriers and cause inflammation. Models have been developed to understand the bacterial - BEC interaction that lead to pathogen crossing into the CNS, however, these have been met with challenges due to these highly specialized BEC phenotypes. This perspective provides a brief overview and outlook of the in vivo and in vitro models currently being used to study bacterial brain penetration, and opinion on improved models for the future.


Potential for pre-implantation determination of human platelet antigen type using DNA amplification: a strategy for prevention of allo-immune thrombocytopenia.
To demonstrate that fetal human platelet antigen (HPA1) type can be determined by amplification from picogram quantities of DNA, nested oligonucleotide DNA primers were designed to amplify a portion of the platelet glycoprotein GpIIIa gene which spans the polymorphic HPA site. Specific oligonucleotides were designed to hybridise either to the amplified HPA1a allele or to the HPA1b allele. DNA dilutions were used as a template and HPA1 type, determined by this method from as little as 2 pg of DNA in 6 cases, was compared to direct typing of blood from the same individuals. In each case nested polymerase chain reaction amplified the specific HPA locus from as little as 2 pg of DNA and determination of HPA1 type agreed with typing of blood.


Low prevalence of fks1 hot spot 1 mutations in a worldwide collection of Candida strains.
We evaluated the prevalence of fks1 hot spot (HS) 1 mutations among 133 Candida strains from six species displaying various caspofungin MIC values (from < or =0.008 to >8 microg/ml). Only 4 (2.9%) strains displayed FKS1 HS1 amino acid substitutions: 1 C. albicans (F641Y) among 32 isolates tested (3.1%), 1 C. glabrata (S645P) among 34 isolates tested (2.9%), and 2 C. tropicalis (F641S) among 12 isolates tested (16.7%). The 4 isolates displaying FKS1 HS1 alterations showed elevated caspofungin MIC results (1 to >8 microg/ml) but lower anidulafungin and micafungin MIC values (0.12 to 4 microg/ml and 0.25 to 4 microg/ml, respectively) in some instances within the wild-type MIC population, as determined using the epidemiologic cutoff values (ECV). Candida krusei, C. parapsilosis, and C. guilliermondii isolates tested showed no FKS1 HS1 alterations regardless of echinocandin MIC result. We additionally analyzed 8 C. albicans and 7 C. glabrata strains for mutations on other HS regions of fks1 and fks2. Three C. glabrata strains showed alterations on FKS2 HS1 (two S645P and one L644W). In general, strains displaying S645P alteration showed higher echinocandin MIC values than strains harboring other mutations. Overall, Candida spp. strains showing caspofungin MIC values within the ECV did not display fks HS mutations. In contrast, strains showing alterations in this region displayed anidulafungin and/or micafungin MIC values within the wild-type population, suggesting that caspofungin could be the most sensitive agent for detection of these resistance mutations. Furthermore, results from this large, geographically diverse Candida spp. collection demonstrated that fks1 HS1 mutations remain uncommon among isolates with various echinocandin MIC levels.


Long-term reduction of T-cell intracellular antigens reveals a transcriptome associated with extracellular matrix and cell adhesion components.
Knockdown of T-cell intracellular antigens TIA1 and TIAR contributes to a cellular phenotype characterised by uncontrolled proliferation and tumorigenesis. Massive-scale poly(A+) RNA sequencing of TIA1 or TIAR-knocked down HeLa cells reveals transcriptome signatures comprising genes and functional categories potentially able to modulate several aspects of membrane dynamics associated with extracellular matrix and focal/cell adhesion events. The transcriptomic heterogeneity is the result of differentially expressed genes and RNA isoforms generated by alternative splicing and/or promoter usage. These results suggest a role for TIA proteins in the regulation and/or modulation of cellular homeostasis related to focal/cell adhesion, extracellular matrix and membrane and cytoskeleton dynamics.


[Effects and mechanism of the long-snake moxibustion on ankylosing spondylitis based on Th17/Treg/Th1 immune imbalance].
To explore the effects and mechanisms of the long-snake moxibustion on ankylosing spondylitis (AS) based on Th17/Treg/Th1 immune imbalance. A total of 60 AS patients were randomized into an observation group and a control group, 30 cases in each one. In the observation group, the long-snake moxibustion therapy was used on the acupoints of the governor vessel from Dazhui (GV 14) to Yaoshu (GV 2) as well as the bilateral Jiaji (EX-B 2) alternatively. The moxibustion was given once a day, for 7 days continuously as one course. There were 3 days at the interval between the courses and 4 courses were required. In the control group, the routine western medication was provided, the salazosulfapyridine combined with non-steroidal anti-inflammatory drugs were used, for 7 days continuous as one course. A total of 4 courses of medication were required. The enzyme linked immunosorbent assay (ELISA) was adopted to determine the levels of interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23) and tumor necrosis factor-α (TNF-α). The real-time quantification polymerase chain reaction (RT-PCR) was used to determine the mRNA expressions of the specific transcription factors, FoxP3 and T-bet of the helper 17 cells (Th17), regulatory T cells (Treg) and T helper 1 cells (Th1). The flow cytometry was applied to determine the rates of Treg, Th1 and Th17, as well as the changes of the inflammatory reaction index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The therapeutic effects were compared between the two groups. After treatment, the total effective rate was 93.3% (28/30) in the observation group, which was better than 86.7% (26/30) in the control group (P<0.05). After treatment, the levels of CRP, ESR, IL-6, IL-17, IL-23 and TNF-α, as well as the rate of Th17 were reduced significantly as compared with those before treatment in the observation group (all P<0.05). The mRNA expressions of FoxP3 and T-bet and the rates of Treg and Th1 were increased as compared with those before treatment (all P<0.05). The change degree in the observation group was significant as compared with the control group (all P<0.05). In the control group, the levels of CRP, ESR, IL-6, IL-17, IL-23 and TNF-α, as well as the rate of Th17 were reduced, and the mRNA expressions of FoxP3 and T-bet and the rates of Treg and Th1 were increased after treatment. But the changes were not significant as compared with those before treatment (all P>0.05). The long-snake moxibustion effectively relieves the clinical symptoms in AS patients and regulates the Th17/Treg/Th1 immune imbalance. Its effect target is probably related to the modulation of the AS immune derangement and the inflammatory responses induced by immune derangement so as to achieve the dual-positive regulatory effect.


Effects of (18)O isotopic substitution on the rotational spectra and potential splitting in the OH-OH2 complex: improved measurements for (16)OH-(16)OH2 and (18)OH-(18)OH2, new measurements for the mixed isotopic forms, and ab initio calculations of the (2)A'-(2)A" energy separation.
Rotational spectra have been observed for (16)OH-(16)OH(2), (16)OH-(18)OH(2), (18)OH-(16)OH(2), and (18)OH-(18)OH(2) with complete resolution of the nuclear magnetic hyperfine structure from the OH and water protons. Transition frequencies have been analyzed for each isotopic form using the model of Marshall and Lester [J. Chem. Phys. 121, 3019 (2004)], which accounts for partial quenching of the OH orbital angular momentum and the decoupling of the electronic spin from the OH molecular axis. The analysis accounts for both the ground ((2)A(')) and first electronically excited ((2)A(")) states of the system, which correspond roughly to occupancy by the odd electron in the p(y) and p(x) orbitals, respectively (where p(y) is in the mirror plane of the complex and p(x) is perpendicular to p(y) and the OH bond axis). The spectroscopic measurements yield a parameter, rho, which is equal to the vibrationally averaged (2)A(')-(2)A(") energy separation that would be obtained if spin-orbit coupling and rotation were absent. For the parent species, rho = -146.560 27(9) cm(-1). (18)O substitution on the water increases /rho/ by 0.105 29(10) cm(-1), while substitution on the OH decreases /rho/ by 0.068 64(11) cm(-1). In the OH-OH(2) complex, the observed value of rho implies an energy spacing between the rotationless levels of the (2)A(') and (2)A(") states of 203.76 cm(-1). Ab initio calculations have been performed with quadratic configuration interaction with single and double excitations (QCISD), as well as multireference configuration interaction (MRCI), both with and without the inclusion of spin-orbit coupling. The MRCI calculations with spin-orbit coupling perform the best, giving a value of 171 cm(-1) for the (2)A(')-(2)A(") energy spacing at the equilibrium geometry. Calculations along the large-amplitude bending coordinates of the OH and OH(2) moieties within the complex are presented and are shown to be consistent with a vibrational averaging effect as the main cause of the observed isotopic sensitivity of rho.


Antisense oligodeoxynucleotide to delta opioid receptors blocks cocaine-induced place preference in mice.
The effect of intracerebroventricular (i.c.v.) treatment with antisense oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on cocaine-induced place preference was examined in mice. Cocaine (10 mg/kg, s.c.) produced a significant place preference. I.c.v. treatment with A-oligo (0.001-1 microg/mouse) dose-dependently attenuated the cocaine (10 mg/kg, s.c.)-induced place preference, although mismatched oligodeoxynucleotide (1 microg/mouse, i.c.v.) was ineffective. In the present study, we found that the selective reduction in number and/or function of central delta opioid receptors by A-oligo suppresses the cocaine-induced place preference. These results suggest that the conditioned reward by cocaine may be partially mediated by central delta opioid receptors.


A Systems Biology Approach to Understanding the Mechanisms of Action of an Alternative Anticancer Compound in Comparison to Cisplatin.
Many clinically available anticancer compounds are designed to target DNA. This commonality of action often yields overlapping cellular response mechanisms and can thus detract from drug efficacy. New compounds are required to overcome resistance mechanisms that effectively neutralise compounds like cisplatin and those with similar chemical structures. Studies have shown that 56MESS is a novel compound which, unlike cisplatin, does not covalently bind to DNA, but is more toxic to many cell lines and active against cisplatin-resistant cells. Furthermore, a transcriptional study of 56MESS in yeast has implicated iron and copper metabolism as well as the general yeast stress response following challenge with 56MESS. Beyond this, the cytotoxicity of 56MESS remains largely uncharacterised. Here, yeast was used as a model system to facilitate a systems-level comparison between 56MESS and cisplatin. Preliminary experiments indicated that higher concentrations than seen in similar studies be used. Although a DNA interaction with 56MESS had been theorized, this work indicated that an effect on protein synthesis/ degradation was also implicated in the mechanism(s) of action of this novel anticancer compound. In contrast to cisplatin, the different mechanisms of action that are indicated for 56MESS suggest that this compound could overcome cisplatin resistance either as a stand-alone treatment or a synergistic component of therapeutics.


A route toward the generation of thermally stable Au cluster anions supported on the MgO surface.
On the basis of experimental evidence and DFT calculations, we propose a simple yet viable way to stabilize and chemically activate gold nanoclusters on MgO. First the MgO surface is functionalized by creation of trapped electrons, (H (+))(e (-)) centers (exposure to atomic H or to H 2 under UV light, deposition of low amounts of alkali metals on partially hydroxylated surfaces, etc.); the second step consists in the self-aggregation of gold clusters deposited from the gas phase. The calculations show that the (H (+))(e (-)) centers act both as nucleation and activation sites. The process can lead to thermally stable gold cluster anions whose catalytic activity is enhanced by the presence of an excess electron.


Role of the gut in the development of injury- and shock induced SIRS and MODS: the gut-lymph hypothesis, a review.
It has long been recognized that major trauma, shock, or burn injury can lead to an acute systemic inflammatory state (SIRS) as well as the multiple organ dysfunction syndrome (MODS). Because of the high mortality rate associated with the development of MODS, for over two decades an intense effort has been devoted towards trying to unravel the underlying mechanisms of this complex syndrome. Although the gut has been implicated in the development of SIRS and MODS experimentally and clinically, its exact role in the pathogenesis of SIRS and MODS remains controversial. However, based on recent experimental evidence, it appears that unique gut-derived factors carried in the intestinal lymph, but not the portal vein, lead to acute injury- and shock-induced SIRS and MODS. These observations have led to the gut-lymph hypothesis of MODS, where gut-derived factors present in intestinal (mesenteric) lymph serve as the triggers that initiate the systemic inflammatory and tissue injurious responses observed after major trauma or episodes of shock.


Effect of Teriparatide Treatment on Circulating Periostin and Its Relationship to Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis.
Treatment of postmenopausal osteoporosis with teriparatide parathyroid hormone amino terminal 1-34 increases bone formation and improves bone microarchitecture. A possible modulator of action is periostin. In vitro experiments have shown that periostin might regulate osteoblast differentiation and bone formation through Wnt signaling. The effect of teriparatide on periostin is not currently known. To determine the effect of teriparatide treatment on circulating levels of periostin and other regulators of bone formation and investigate how changes in periostin relate to changes in bone turnover markers, regulators of bone formation, and bone mineral density (BMD). Twenty women with osteoporosis; a 2-year open-label single-arm study. Teriparatide 20 µg was administered by subcutaneous injection daily for 104 weeks. Periostin, sclerostin, and Dickkopf-related protein 1, procollagen type I N-terminal propeptide (PINP), and C-telopeptide of type I collagen were measured in fasting serum collected at baseline (two visits) and then at weeks 1, 2, 4, 12, 26, 52, 78, and 104. BMD was measured at the lumbar spine, total hip, and femoral neck using dual energy x-ray absorptiometry. Periostin levels increased by 6.6% [95% confidence interval (CI), -0.4 to 13.5] after 26 weeks of teriparatide treatment and significantly by 12.5% (95% CI, 3.3 to 21.0; P < 0.01) after 52 weeks. The change in periostin correlated positively with the change in the lumbar spine BMD at week 52 (r = 0.567; 95% CI, 0.137 to 0.817; P < 0.05) and femoral neck BMD at week 104 (r = 0.682; 95% CI, 0.261 to 0.885; P < 0.01). Teriparatide therapy increases periostin secretion; it is unclear whether this increase mediates the effect of the drug on bone.


Dark Matter Freeze-Out via Catalyzed Annihilation.
We present a new paradigm of dark matter freeze-out, where the annihilation of dark matter particles is catalyzed. We discuss in detail the regime in which the depletion of dark matter proceeds via 2χ→2A^{'} and 3A^{'}→2χ processes, where χ and A^{'} denote dark matter and the catalyst, respectively. In this regime, the dark matter number density is depleted polynomially rather than exponentially (Boltzmann suppression) as in classical weakly interacting massive particles and strongly interacting massive particles. The paradigm applies for a secluded weakly interacting dark sector with dark matter in the MeV-TeV mass range. The catalyzed annihilation paradigm is compatible with cosmic microwave background and big bang nucleosynthesis constraints, with enhanced indirect detection signals.


Clinical characteristics of hepatocellular carcinoma with an extensive lymph node metastasis at diagnosis.
Lymph node metastasis is reported to occur only rarely in patients with hepatocellular carcinoma (HCC). However, we have encountered patients with HCC with extensive lymph node metastases. Here we report the clinical characteristics of HCC associated with extensive lymph node metastasis at diagnosis. Ten patients with HCC in whom extensive lymph node metastases were observed at the initial medical examination were studied. The degree of disease progression was documented with ultrasonography and dynamic computed tomography. Primary liver lesions were classified in the following three types according to imaging characteristics: type A, massive type with portal vein tumor thrombus; type B, multinodular, nonencapsulated type; and type C: multinodular, encapsulated type. In patients with types A and B HCC, a large number of lymph node metastases was observed, whereas a small number of isolated metastases was observed in patients with type C. All patients with types A and B HCC died within 7 months (median survival, 4 months), whereas those with type C survived for 4 years or more after treatment with transcatheter arterial chemoembolization and surgery. A relationship exists between the type of primary HCC lesions and the pattern of lymph node metastasis. Long-term survival may be expected for patients with isolated lymph node metastases.


Gathering policymakers' perspectives as an essential step in planning and implementing palliative care services at a national level: an example from a resource-limited country.
Despite increasing recognition of the role played by palliative care (PC) services, the priorities of policymakers in supporting PC remain unclear and have sometimes engendered controversy. There are few studies exploring policymakers' perspectives towards PC services, with most shedding light on obstacles to PC development. Furthermore, no study has explored policymakers' perspectives towards providing PC at the national level in resource-limited countries. This study provides a platform for providing PC as part of the Palestinian healthcare system (HCS) by exploring policymakers' perspectives on PC, an essential step to developing a PC programme. A descriptive qualitative study design was employed using semi-structured interviews. Participants were those identified as responsible for making executive and legislative decisions about health services (including PC) in the HCS. Data were analysed using qualitative content analysis. Twelve decision and policymakers participated in the study. Four categories were generated from the content analysis: (1) the nature of current PC healthcare services, (2) the potential benefits of PC, (3) challenges to providing PC, and (4) considerations in providing PC. The current PC services provided to Palestinian patients with life-limiting illnesses and their families are not comprehensive, and are limited to symptom management. There is a Palestinian national strategic plan for developing PC; however, the development goals are not clearly defined, and the plan's capabilities are inadequate. Several challenges to the provision of PC were found to relate to issues of education and training, the allocation of funding, and the availability of medications. Integrating PC into the Palestinian university curricula as a compulsory course and establishing higher degree programmes in PC to overcome the shortage of PC specialists is required. Developing policies aligned with national laws could help enhance health services to patients and their families and resolve several challenges. Cooperating with national and international institutions in seeking funding could boost PC development and medication availability.