24(S),25-Epoxycholesterol and cholesterol 24S-hydroxylase (CYP46A1) overexpression promote midbrain dopaminergic neurogenesis in vivo.
The liver X receptors Lxrα/NR1H3 and Lxrβ/NR1H2 are ligand-dependent nuclear receptors critical for midbrain dopaminergic (mDA) neuron development. We found previously that 24(S),25-epoxycholesterol (24,25-EC), the most potent and abundant Lxr ligand in the developing mouse midbrain, promotes mDA neurogenesis in vitro In this study, we demonstrate that 24,25-EC promotes mDA neurogenesis in an Lxr-dependent manner in the developing mouse midbrain in vivo and also prevents toxicity induced by the Lxr inhibitor geranylgeranyl pyrophosphate. Furthermore, using MS, we show that overexpression of human cholesterol 24S-hydroxylase (CYP46A1) increases the levels of both 24(S)-hydroxycholesterol (24-HC) and 24,25-EC in the developing midbrain, resulting in a specific increase in mDA neurogenesis in vitro and in vivo, but has no effect on oculomotor or red nucleus neurogenesis. 24-HC, unlike 24,25-EC, did not affect in vitro neurogenesis, indicating that the neurogenic effect of 24,25-EC on mDA neurons is specific. Combined, our results indicate that increased levels of 24,25-EC in vivo, by intracerebroventricular delivery in WT mice or by overexpression of its biosynthetic enzyme CYP46A1, specifically promote mDA neurogenesis. We propose that increasing the levels of 24,25-EC in vivo may be a useful strategy to combat the loss of mDA neurons in Parkinson's disease.


Concomitant high expression of ERα36, GRP78 and GRP94 is associated with aggressive papillary thyroid cancer behavior.
Papillary thyroid cancer (PTC) is more common in women than in men. It has been suggested that estrogen may be involved in its development, as has previously been shown for breast, endometrial and ovarian cancer. The purpose of this study was to assess correlations between the expression of the estrogen receptor alpha36 (ERα36) and the glucose regulated proteins GRP78 and GRP94 (chaperones involved in glycoprotein folding) and various PTC clinicopathological features, as well as to evaluate the potential usefulness of these three potential oncogenic proteins in the prediction of aggressive PTC behavior. ERα36, GRP78 and GRP94 protein expression in 218 primary PTC tissues and PTC-derived BCPAP cells was examined using immunohistochemistry, Western blotting and immunocytochemistry. The proliferative, invasive and migrative capacities of BCPAP cells in which the respective genes were either exogenously over-expressed or silenced were assessed using BrdU incorporation and Transwell assays, respectively. We found that ERα36, GRP78 and GRP94 protein expression was upregulated in the primary PTC tissues tested. We also found that ERα36, GRP78 and GRP94 expression modulation affected the proliferation, invasion and migration of PTC-derived BCPAP cells. A positive correlation and a positive feedback loop were noted between ERα36, GRP78 and GRP94 protein expression in the primary PTC tissues and in BCPAP cells, respectively. High ERα36 expression in combination with a high GRP78/ GRP94 expression was found to have a stronger correlation with extrathyroid extension (ETE), lymph node metastasis (LNM), distant metastasis (DM) and high TNM stage than high ERα36 expression in combination with either high GRP78 or high GRP94 expression (p = 0.028 for ETE, p = 0.002 for DM and p ≤ 0.001 for LNM and high TNM stage) or high ERα36 expression alone (p < 0.001 for ETE, LNM, DM and high TNM stage). From our data we conclude that a concomitant high expression of ERα36, GRP78 and GRP94 is strongly associated with aggressive PTC behavior and may be used as a predictor for ETE, LNM, DM and high TNM stage.


Selective Electrocatalytic Reduction of Nitrite to Dinitrogen Based on Decoupled Proton-Electron Transfer.
The development of denitrification catalysts which can reduce nitrate and nitrite to dinitrogen is critical for sustaining the nitrogen cycle. However, regulating the selectivity has proven to be a challenge, due to the difficulty of controlling complex multielectron/proton reactions. Here we report that utilizing sequential proton-electron transfer (SPET) pathways is a viable strategy to enhance the selectivity of electrochemical reactions. The selectivity of an oxo-molybdenum sulfide electrocatalyst toward nitrite reduction to dinitrogen exhibited a volcano-type pH dependence with a maximum at pH 5. The pH-dependent formation of the intermediate species (distorted Mo(V) oxo species) identified using operando electron paramagnetic resonance (EPR) and Raman spectroscopy was in accord with a mathematical prediction that the pKa of the reaction intermediates determines the pH-dependence of the SPET-derived product. By utilizing this acute pH dependence, we achieved a Faradaic efficiency of 13.5% for nitrite reduction to dinitrogen, which is the highest value reported to date under neutral conditions.


Alterations of senescence biomarkers in human cells by exposure to CrVI in vivo and in vitro.
Heavy metals like CrVI, CdII, PbII and SnII have many applications in industry. They also represent a group of labour pollutants, as they are involved in several physiological disorders, such as carcinogenesis and various tissue dysfunctions. However, limited knowledge exists regarding their effects on ageing. In the current work we provide evidence that workers chronically exposed to CrVI have considerably reduced serum levels of the biomarker of senescence and cell survival, Apolipoprotein J/Clusterin (ApoJ/CLU). Moreover, we have found that both the degree and the time of exposure to CrVI associate negatively with ApoJ/CLU serum levels. To further examine whether CrVI directly affects cellular senescence we treated for 10 weeks two adult skin fibroblasts cultures as well as embryonic fibroblasts with a range of CrVI concentrations that approximate the values recorded in the blood circulation of exposed workers. Cellular treatment with a CrVI concentration that approximates the highest concentration in the blood was extremely toxic and nearly all cells died immediately after the first treatment. Interestingly, continuous treatment with a 10-fold lower CrVI concentration resulted in the induction of premature senescence. More specifically, treated cells were growth arrested, acquired an irregular shape, were positive to beta-galactosidase staining, accumulated oxidized proteins and over-expressed the cyclin-dependent kinase inhibitor p21 and ApoJ/CLU. Similar treatments with three additional labour pollutants resulted in the induction of premature senescence by CdII, but not by SnII or PbII. In summary, our results indicate that exposure to CrVI induces alterations of senescence biomarkers both in vivo and in vitro. They also provide new valuable tools for monitoring CrVI cytotoxic effects in vivo as well as for re-evaluating the maximum permissive values of some labour pollutants, like CrVI and CdII.


[Inhibitive effect of acanthopanax senticosus injection on gentamicin-induced ototoxicity in guinea pigs].
To study the antagonistic action of acanthopanax senticosus injection (ASS) on gentamicin ototoxicity. Guinea pigs were randomly divided into control group, GM group, ASS group, and ASS + GM group. The changes of hearing threshold, cochlear morphology, expression of caspases-3 were determined by ABR, TEM, and Western blot, respectively. The ABR threshold in GM group increased markedly. There was no significant difference in ABR threshold between ASS group and control group, but the ABR threshold in ASS group was much lower than that both in GM group and ASS + GM group. Severely injured hair cells with morphological characteristics of apoptosis were found under TEM in GM group, and the hair cells were less injured in ASS + GM group. The results of Western blot showed that the expression of caspase-3 increased markedly in GM group, but it increased slightly in ASS + GM group. ASS may antagonize the GM ototoxicity by inhibiting the expression of caspases-3.


Population structure of Squatina guggenheim (Squatiniformes, Squatinidae) from the south-western Atlantic Ocean.
Population genetic analyses based on both mitochondrial cytochrome b and the internal transcribed spacer 2 of recombinant (r)DNA genes were implemented to examine hypotheses of population differentiation in the angular angel shark Squatina guggenheim, one of the four most-widespread endemic species inhabiting coastal ecosystems in the south-western Atlantic Ocean. A total of 82 individuals of S. guggenheim from 10 sampling sites throughout the Río de la Plata mouth, its maritime front, the outer shelf at the subtropical confluence and the coastal areas of the south-west Atlantic Ocean, were included. The analysis of molecular variance (AMOVA) based on the second internal transcribed spacer (its-2) region supports that the samples from the outer shelf represent an isolated group from other sites. Historical gene flow in a coalescent-based approach revealed significant immigration and emigration asymmetry between sampling sites. Based on the low level of genetic diversity, the existence of a long-term population decline or a past recent population expansion following a population bottleneck could be proposed in S. guggenheim. This demographic differentiation suggests a degree of vulnerability to overexploitation in this endemic and endangered south-west Atlantic Ocean shark, given its longevity and low reproductive potential.


Comparison of Collum Angle of Maxillary Central Incisors in Different Incisor Relationships.
To compare the collum angle of maxillary central incisors in patients with different incisor relationships. Comparative, cross-sectional study. Department of Orthodontics, Armed Forces Institute of Dentistry, Combined Military Hospital, Rawalpindi, from March to October 2019. Patient data was obtained from the Department of Orthodontics, Armed Forces Institute of Dentistry, Rawalpindi. One Hundred patients were included in the study, which were divided into four groups, 25 patients in each group, based on incisor relationship, i.e. class I, class II div 1, class II div 2, and class III. The collum angle of maxillary central incisors was then measured twice by a single investigator on lateral cephalograms. Sagittal skeletal relationship, age and gender were noted. Molar relationship of the above groups was also recorded from their respective casts. Out of the 100 patients, 31 were males, while 69 were females. Mean collum angles of maxillary central incisors for class I, class II div 1, class II div 2, and class III were 5.12 ±3.78, 6.09 ±4.57, 15.02 ±7.99, and 6.94 ±3.80, respectively. Collum angle of class II div 2 incisor relationship was significantly greater than other classes (p <0.05). Collum angle of incisors of casts with class II molar relationship also exhibited the same trend, i.e. a greater angle than other groups (p=0.002). There was no significant difference in collum angle among different sagittal skeletal relationships (p=0.476), between males and females (p-value .731) and among different age groups (p=0.194). ICC showed good agreement between the readings of collum angle (Crohnbachs Alpha .997). Class II div 2 incisor relationship had a significantly greater collum angle than other groups. Key Words: Collum angle, Incisor inclination, Crown to root angle, Class II div 2 malocclusion.


Impact of the First Generation of Children's Oncology Group Clinical Trials on Clinical Practice for Wilms Tumor.
Refinements in surgery, radiation therapy, and chemotherapy since the mid-20th century have resulted in a survival rate exceeding 90% for patients with Wilms tumor (WT). Although this figure is remarkable, a significant proportion of patients continue to have event-free survival (EFS) estimates of <75%, and nearly 25% of survivors experience severe chronic medical conditions. The first-generation Children's Oncology Group (COG) renal tumor trials (AREN '0'), which opened to enrollment in 2006, focused on augmenting treatment regimens for WT subgroups with predicted EFS <75% to 80%, including those with the adverse prognostic marker of combined loss of heterozygosity (LOH) at chromosomes 1p/16q, pulmonary metastasis with incomplete lung nodule response after 6 weeks of chemotherapy, bilateral disease, and anaplastic histology. Conversely, therapy was reduced for patient subgroups with good outcomes and potential for long-term toxicity, such as those with lung metastasis with complete lung nodule response after 6 weeks of chemotherapy. This article summarizes the key findings of the first-generation COG renal tumor studies and their implications for clinical practice.


Spatial, seasonal and climatic predictive models of Rift Valley fever disease across Africa.
Understanding the emergence and subsequent spread of human infectious diseases is a critical global challenge, especially for high-impact zoonotic and vector-borne diseases. Global climate and land-use change are likely to alter host and vector distributions, but understanding the impact of these changes on the burden of infectious diseases is difficult. Here, we use a Bayesian spatial model to investigate environmental drivers of one of the most important diseases in Africa, Rift Valley fever (RVF). The model uses a hierarchical approach to determine how environmental drivers vary both spatially and seasonally, and incorporates the effects of key climatic oscillations, to produce a continental risk map of RVF in livestock (as a proxy for human RVF risk). We find RVF risk has a distinct seasonal spatial pattern influenced by climatic variation, with the majority of cases occurring in South Africa and Kenya in the first half of an El Niño year. Irrigation, rainfall and human population density were the main drivers of RVF cases, independent of seasonal, climatic or spatial variation. By accounting more subtly for the patterns in RVF data, we better determine the importance of underlying environmental drivers, and also make space- and time-sensitive predictions to better direct future surveillance resources.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'.


Simultaneous and visual detection of infectious bronchitis virus and Newcastle disease virus by multiple LAMP and lateral flow dipstick.
Infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) are both important viruses seriously affecting poultry industry worldwide. In this study, reverse-transcription LAMP (RT-LAMP) was combined with lateral flow dipstick (LFD) forming a novel detection tool which could simultaneously detect IBV and NDV visually. Primers targeted the 5'-untranslated region (5'-UTR) of IBV genome and the conserved region of NDV large polymerase gene (LP). The specificity and sensitivity of this multiple reverse transcription-LAMP-LFD (mRT-LAMP-LFD) assay were compared with those of conventional RT-PCR, nested RT-PCR (nRT-PCR), quantification RT-PCR (qRT-PCR), and RT-LAMP monitored by electrophoresis. No non-specific amplifications were observed when the assays were tested with unrelated viruses. According to the sensitivity study, when detecting IBV or NDV alone, the lowest detection limits of mRT-LAMP-LFD were 100.8 IBV RNA copies/reaction and 100.7 NDV RNA copies/reaction. Furthermore, when detecting IBV and NDV simultaneously, the lowest detection limit was the same as that of the single detection assays. In the clinical sample study, mRT-LAMP-LFD performed the best among these assays. When tested with IBV or NDV single infected samples, the mean detection rates were 98.65% and 97.25%, respectively. In the IBV and NDV co-infected sample study, the mean detection rates of IBV and NDV were both 95%. This study showed that mRT-LAMP-LFD was a promising qualitative detection tool suitable for field single or multiple IBV and NDV detection.


Selective preparation of macroporous monoliths of conductive titanium oxides Ti(n)O(2n-1) (n = 2, 3, 4, 6).
Monolithic conductive titanium oxides Ti(n)O(2n-1) (n = 2, 3, 4, 6) with well-defined macropores have been successfully prepared as a single phase, via reduction of a macroporous TiO(2) precursor monolith using zirconium getter. Despite substantial removal of oxide ions, all the reduced monoliths retain the macropore properties of the precursor, i.e., uniform pore size distribution and pore volume. Furthermore, compared to commercial porous Ebonex (shaped conductive Ti(n)O(2n-1)), the bulk densities (1.8 g cm(-3)) are half, and the porosities (60%) are about 3 times higher. The obtained Ti(n)O(2n-1) (n = 2, 3, 4, 6) macroporous monoliths could find applications as electrodes for many electrochemical reactions.


Regulation of follistatin production by rat granulosa cells in vitro.
The aims of this study were to apply enzyme-linked immunosorbent assays (ELISA) for human follistatins (FS) to measure total immunoreactive (ir-) rat FS and free rat FS, and investigate the regulation of production of total ir-FS and free FS by rat granulosa cells (GC) in vitro. Production of ir-inhibin was monitored as an index of GC function. The ELISAs for total ir-FS, based on an immunoradiometric assay developed recently for human FS, and free FS, based on capture of FS by a monoclonal antibody and detection by activin A binding, had sensitivities of 0.4 and 0.8 ng recombinant human (rh-) FS 288/ml, respectively, and did not cross-react with inhibin A, rLH, or FSH. rh-Activin did not cross react in the total ir-FS ELISA, but interfered with the measurement of free FS. Dilutions of GC-conditioned medium were parallel to the standard curve of rh-FS 288 for each assay. The values obtained in the free FS assay were 10- to 20-fold higher than those in the total ir-FS ELISA, suggesting that rat FS may be recognized by the antibodies differently than the human standard. Both total ir-FS and free FS production by undifferentiated GC from diethylstilbestrol (DES)-treated, immature rats increased with cell number and time in culture and were stimulated dose dependently by FSH, rh-activin A (except free FS, which was not measured because of interference), forskolin, and phorbol 12-myristrate. The effects of FSH and activin on FS production by undifferentiated GC were additive. There were significant effects of degree of differentiation of GC on basal FS production and responsiveness to FSH, LH, and rh-activin A. Both total ir-FS and free basal FS production increased up to 4-fold with the degree of differentiation of GC, produced by treating rats in vivo with DES (undifferentiated), DES plus FSH (partially differentiated), or DES plus FSH plus hCG (fully differentiated). The addition of FSH in vitro increased FS production by undifferentiated and partially differentiated GC, but not by fully differentiated GC. The only detectable effect of LH on FS production was on partially differentiated GC. Activin A stimulated total ir-FS production by undifferentiated and partially differentiated GC, but inhibited total ir-FS production by fully differentiated GC. Ir-inhibin production in these experiments was similar to that of FS with the following exceptions; phorbol 12-myristrate inhibited ir-inhibin production by undifferentiated GC, basal ir-inhibin decreased in fully differentiated GC, FSH stimulated ir-inhibin only in undifferentiated GC, and rh-activin A stimulated ir-inhibin at all stages. It is concluded that 1) FS protein production by cultured undifferentiated rat GC is up-regulated by FSH and activin, possibly via both protein kinase A and C pathways; 2) increasing GC differentiation is associated with a significant increase in basal FS production by rat GC and a change in the hormonal regulation of FS production; and 3) FS and ir-inhibin production by cultured rat GC can be differentially regulated. The results are consistent with the hypothesis that activin tone decreases within follicles as they develop due to increased production of the activin-binding protein FS.


[Variations in topsoil carbon and nitrogen contents of five temperate plantations in Northeast China.]
Afforestation is an effective way for carbon (C) sequestration, which also profoundly influences soil nitrogen (N) dynamics in the forest ecosystem. The impacts of tree species on soil C and N budgets and the underlying mechanism remain uncertain. In this study, we used a common garden experiment and measured the soil organic C (Csoil) and total N contents (Nsoil) of the topsoil (0-10 cm) and related vegetative and soil microbial properties in 2007 and 2015 (3 and 11 years after afforestation), respectively. Our aim was to explore the effects of five major tree species (i.e., Fraxinus mandshurica, Juglans mandshurica, Betula platyphylla, Larix gmelinii and Pinus sylvestris var. mongolica) in the temperate forests in Northeast China on soil C and N contents and their dri-vers. The results showed that both Csoil and Nsoil of the five stands decreased as the stand ages increased, the change rates of which were significantly correlated with each other. The rate of change in Csoil(2.6%·a-1-4.8%·a-1) was significantly greater than that in Nsoil(0.8%·a-1-2.8%·a-1). The decrements of the Csoil and Nsoil for the broadleaved stands were significantly lower than those of the coniferous stands. The tree-species traits and microbial properties together explained 68.5% and 90.9% of the variability of the change rates of Csoil and Nsoil, respectively. The change rates of Csoil and Nsoil decreased with the increases in leaf litter C/N and microbial biomass C/N, but increased with the increases of fine root biomass, microbial biomass C, and the ratio of the C-acquisition to the N-acquisition enzyme activity. Additionally, the change rate of Nsoil decreased with the increases of the leaf litter production and the microbial metabolic activity. Our findings indicated that C and N contents in the topsoil of these temperate plantations decreased significantly 11 years after afforestation, while the different change rates mainly resulted from different properties of tree species and soil microbes.


Efficient CO2 fixation into cyclic carbonates catalyzed by NNO-scorpionate zinc complexes.
A series of new chiral zwitterionic NNO-scorpionate mononuclear zinc alkyls [Zn(R)(κ3-NNO)]Br was developed in very high yields via suitable quaternization in the scorpionate ligand. These zwitterionic complexes performed as bifunctional catalysts and exhibited improved catalytic activity for the fixation of CO2 into cyclic carbonates compared to the neutral analog mononuclear [Zn(R)(κ3-NNO)] and binuclear [Zn(R)(κ2-NNμ-O)Zn(R)2] compounds. The catalyst system showed a broad substrate scope and functional group tolerance under mild and solvent-free conditions.


Accelerated biodegradation of BPA in water-sediment microcosms with Bacillus sp. GZB and the associated bacterial community structure.
Bisphenol A (BPA) is a synthetic chemical primarily used to produce polycarbonate plastics and epoxy resins. Significant industrial and consumer's consumption of BPA-containing products has contributed to extensive contamination in different environmental matrices. In this study, microcosms bioaugmented with Bacillus sp. GZB were constructed to investigate BPA biodegradation, identify the main bacterial community, and evaluate bacterial community responses in the microcosms. Under aerobic conditions, BPA was quickly depleted as a result of bioaugmentation with Bacillus sp. GZB in water-sediment contaminated with pollutants. The pollutants used were generally associated with the electronic wastes (mobile phones, computers, televisions) dismantling process. Adding BPA affected the bacterial community composition in the water-sediment. Furthermore, BPA biodegradation was enhanced by adding electron donors/co-substrates: humic acid, NaCl, glucose, and yeast extract. Metagenomic analysis of the total 16S rRNA genes from the BPA-degrading microcosms with bioaugmentation illustrated that the genera Bacillus, Thiobacillus, Phenylobacterium, and Cloacibacterium were dominant after a 7-week incubation period. A consortium of microorganisms from different bacterial genera may be involved in BPA biodegradation in electronic waste contaminated water-sediment. This study provides new insights about BPA bioaugmentation and bacterial ecology in the BPA-degrading environment.


Normal visual field test results following glaucomatous visual field end points in the Ocular Hypertension Treatment Study.
To compare the occurrence of normal visual field (VF) test results following 2 vs 3 consecutive, abnormal, reliable test results in the Ocular Hypertension Treatment Study. The Ocular Hypertension Treatment Study is a prospective, multicenter follow-up study as part of a longitudinal randomized clinical trial. Sixty-four (68 eyes) of 1636 participants developed a VF primary open-angle glaucoma (POAG) end point. We compared the proportion of normal VF test results after a VF POAG end point among eyes whose VF abnormality was confirmed by 2 (n = 9 eyes) vs 3 (n = 59 eyes) consecutive, abnormal, reliable VF test results. The proportion of VF test results that were normal subsequent to a VF POAG end point in eyes whose abnormality was confirmed by 2 consecutive, abnormal, reliable test results was significantly higher (73 [66%] of 110) compared with eyes whose abnormality was confirmed by 3 consecutive, abnormal, reliable test results (46 [12%] of 381) (P = .01). A VF POAG end point confirmed by 3 consecutive, abnormal, reliable VF test results appears to have greater specificity and stability than either 1 or 2 consecutive, abnormal, reliable VF test results. However, some eyes whose VF POAG end point was confirmed by 3 consecutive, abnormal, reliable test results nonetheless had 1 or more normal test results on follow-up.


Additional Effect of Static Ultrasound and Diadynamic Currents on Myofascial Trigger Points in a Manual Therapy Program for Patients With Chronic Neck Pain: A Randomized Clinical Trial.
To assess the additional effect of static ultrasound and diadynamic currents on myofascial trigger points in a manual therapy program to treat individuals with chronic neck pain. A single-blind randomized trial was conducted. Both men and women, between ages 18 and 45, with chronic neck pain and active myofascial trigger points in the upper trapezius were included in the study. Subjects were assigned to 3 different groups: group 1 (n = 20) was treated with manual therapy; group 2 (n = 20) was treated with manual therapy and static ultrasound; group 3 (n = 20) was treated with manual therapy and diadynamic currents. Individuals were assessed before the first treatment session, 48 hours after the first treatment session, 48 hours after the tenth treatment session, and 4 weeks after the last session. There was no group-versus-time interaction for Numeric Rating Scale, Neck Disability Index, Pain-Related Self-Statement Scale, pressure pain threshold, cervical range of motion, and skin temperature (F-value range, 0.089-1.961; P-value range, 0.106-0.977). Moreover, we found no differences between groups regarding electromyographic activity (P > 0.05). The use of static ultrasound or diadynamic currents on myofascial trigger points in upper trapezius associated with a manual therapy program did not generate greater benefits than manual therapy alone.


Are psychologists willing and able to promote physical activity as part of psychological treatment?
Physical activity can provide psychological benefits, but there is little research on psychologists' promoting activity as part of psychological treatment. This study assessed psychologists' attitudes to and frequency of providing activity advice and counseling. A mail questionnaire sent to 620 psychologists provided 236 responses (38%). Items assessed frequency of providing activity advice and counseling, confidence to provide activity advice and counseling, perceived efficacy of activity for managing physical and psychological conditions, acceptability of activity advice and counseling, knowledge of national activity guidelines, exposure to training in activity promotion, and practice and sociodemographic characteristics. Data were analysed using descriptive statistics and multiple linear regression analyses. Among respondents, 83% reported often recommending activity, 67% often provided activity advice, and 28% often did activity counseling. There was a high level of acceptability for physical activity promotion as part of psychological treatment. Over 80% of respondents were confident to provide general activity advice, discuss activity options, and problem solve barriers to activity, but less than half were confident to monitor activity levels or to tailor advice. Factors significantly associated with providing activity advice and counseling were: if the psychologist reported doing regular exercise, confidence to provide general activity advice, high acceptability, working in private practice, and clients presenting with general health and well-being issues (p < 0.05). Seventy-two percent of respondents were interested in attending a workshop on providing activity advice and counseling. Many psychologists are willing and potentially able to promote physical activity as part of psychological treatment and would be likely to participate in relevant professional development.


Extreme Ultraviolet Multilayer Defect Compensation in Computational Lithography.
For the extreme ultraviolet (EUV) lithography, multilayer (ML) defects such as bump and pit defects can disrupt the phase of reflected field and degrade aerial images on wafer. In this paper, a defect printability and repair simulator (DPRS) is introduced to predict and repair the effect of ML defects in EUV aerial images. DPRS is composed of multilayer growth by using Gaussian function and Stearns's method, mask simulation by using a scattering matrix (S-matrix) analysis method, and projection simulation by using Köhler's illumination. For bump and pit ML defects, the combining the modified absorber and the layer-by-layer ML peeling is better than other methods. This study can be helpful in understanding EUV defect and also give insight into the EUV defect compensation for the device volume production.


Unusual computed tomography appearance of Castleman disease.
A case is presented here of Castleman disease in an uncommon location. Ultrasonography demonstrated a large hypoechoic mass with multiple vascular channels. On computed tomography, the lesions with a nodular contour were located lateral to the carotid sheath on the right side, and demonstrated a variegated enhancement pattern.


Efferent fibres to the aortic bodies: a search for their cell bodies in the brainstem of the cat and rabbit.
An attempt has been made to determine where in the lower brainstem the cell bodies of nonsympathetic efferent fibres in the aortic nerve of the cat and rabbit are located. Horseradish peroxidase (HRP) was placed on the central end of the right cut aortic nerve of anaesthetized animals and, after an appropriate time, sections of the brainstem encompassing the rostral and caudal limits of the dorsal vagal motor nucleus and nucleus ambiguus were examined microscopically for retrogradely transported HRP. Cell bodies labelled by exogenous HRP were not found in any of the cats or rabbits exposed to HRP although reaction product, due to an endogenous response, was observed. Appropriate control experiments were performed to show that the sensitivity of the technique for demonstrating HRP in our hand was adequate. We conclude that the cell bodies of efferent fibres, of non sympathetic origin, in the aortic nerve are likely to be located outside the central nervous system.


Interscalene brachial plexus block for shoulder surgery in a patient with arthrogryposis multiplex congenita.
A five-year-old child with severe arthrogryposis multiplex congenita and malnutrition underwent surgery for chronic osteomyelitis of the head of the left humerus. The child had typical features of arthrogryposis multiplex congenita, including a difficult airway. Propofol was used for induction and maintenance. Spontaneous respiration was maintained with a nasal airway. Analgesia was provided with an interscalene brachial plexus block placed using a nerve stimulator. No opioid was given. The child had an uneventful recovery with good postoperative analgesia. The anaesthetic implications of arthrogryposis multiplex congenita are discussed.


Intraocular pressure change with eye positions before and after orbital decompression for thyroid eye disease.
To examine intraocular pressure (IOP) changes in primary and upward gazes before and after orbital decompression in patients with thyroid eye disease. Seventy-eight orbits of 40 patients who underwent orbital decompression between June 2010 and September 2012 were retrospectively reviewed. Subjects were divided in 2 groups according to the number of orbital walls removed: deep lateral orbital wall decompression group (Group A) or balanced decompression group (Group B). IOP was measured using Goldmann applanation tonometry in primary gaze and a 20° upward gaze before and 3 months after surgery. Preoperative IOP in upward gaze (18.7 mm Hg) was higher than in primary gaze (15.7 mm Hg, p < 0.001). Postoperative IOP reduction in upward gaze (3.8 mm Hg) was greater than in primary gaze (1.7 mm Hg, p < 0.001). Although the overall postoperative IOP in upward gaze (14.9 mm Hg) remained higher than in primary gaze (14.0 mm Hg, p = 0.038), the gaze-related IOP demonstrated no significant difference in all subgroups (Group A, p = 0.091; Group B, p = 0.332). IOP in upward gaze was higher prior to orbital decompression, but reduction was greater postoperatively and approximated the IOP in primary gaze.


Place of death from dementia as an underlying cause during the COVID-19 pandemic in Japan: a cross-sectional study from national death certificates.
The coronavirus disease (COVID-19) pandemic has challenged palliative end-of-life care for people with dementia. The site of death can be considered as an end-of-life care quality indicator. Most people with dementia prefer to die at nursing or private homes; however, in Japan, they are often hospitalized in psychiatric hospitals for management of neuropsychiatric symptoms. As palliative end-of-life care for older adults with Alzheimer's disease and related dementias has been further challenged by the COVID-19 pandemic, little is known about its effects on the place of death in patients with dementia. This study aimed to investigate the shifts in place of death from dementia during the COVID-19 pandemic in Japan. Changes throughout the pandemic were compared between deaths from dementia and from senility. Cross-sectional. Death certificate data of individuals aged 65 years or older who died in Japan between 1 January 2018, and 31 December 2021, were used to extract the cause and place of death. Differences in place of death between the periods were estimated using multinomial logistic analysis with reference to death in private homes. Deaths from dementia mostly occurred in hospitals (59%), while deaths from senility were most frequent in nursing homes (37%). After adjusting for patient characteristics, the likelihood of hospital deaths significantly increased for patients with dementia during the pandemic. Meanwhile, the likelihood of senility deaths decreased in hospitals but increased in nursing homes during the pandemic. The shift to hospital deaths since the onset of the COVID-19 pandemic was uniquely observed in deaths from dementia. This hospital shift likely involved increased transfers from nursing and private homes to psychiatric hospitals. Further investigation is needed to examine the association between the pandemic-related change in long-term care workforce and palliative care practice in people with dementia.


UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy.
Conventional chemotherapy of pancreatic cancer (PaCa) suffers the problems of low drug permeability and inherent or acquired drug resistance. Development of new strategies for enhanced therapy still remains a great challenge. Herein, we report a new ultrasound-targeted microbubble destruction (UTMD)-promoted delivery system based on dendrimer-entrapped gold nanoparticles (Au DENPs) for co-delivery of gemcitabine (Gem) and miR-21 inhibitor (miR-21i). Methods: In this study, Gem-Au DENPs/miR-21i was designed and synthesized. The designed polyplexes were characterized via transmission electron microscopy (TEM), Gel retardation assay and dynamic light scattering (DLS). Then, the optimum exposure parameters were examined by an ultrasound exposure platform. The cellular uptake, cytotoxicity and anticancer effects in vitro were analyzed by confocal laser microscopy, spectra microplate reader, flow cytometry and a chemiluminescence imaging system. Lastly, the anticancer effects in vivo were evaluated by contrast-enhanced ultrasound (CEUS), hematoxylin and eosin (H&E) staining, TUNEL staining and comparison of tumor volume. Results: The results showed that the Gem-Au DENPs/miR-21i can be uptake by cancer cells and the cellular uptake was further facilitated by UTMD with an ultrasound power of 0.4 W/cm2 to enhance the cell permeability. Further, the co-delivery of Gem and miR-21i with or without UTMD treatment displayed 82-fold and 13-fold lower IC50 values than the free Gem, respectively. The UTMD-promoted co-delivery of Gem and miR-21i was further validated by in vivo treatment and showed a significant tumor volume reduction and an increase in blood perfusion of xenografted pancreatic tumors. Conclusion: The co-delivery of Gem and miR-21i using Au DENPs can be significantly promoted by UTMD technology, hence providing a promising strategy for effective pancreatic cancer treatments.


Evaluation of the role of Carnobacterium piscicola in spoilage of vacuum- and modified-atmosphere-packed cold-smoked salmon stored at 5 degrees C.
The microflora on spoiled cold-smoked salmon often consists of a mixture of lactic acid bacteria (LAB) and Gram-negative bacteria. To elucidate the role of the different groups, a storage trial was carried out in which nisin and CO2 were used for the selective inhibition of the two bacterial groups. The shelf-life of vacuum-packed cold-smoked salmon, recorded by sensory evaluation, was four weeks at 5 degrees C and the microflora was composed of LAB (10(6)-10(7) cfu/g) with an associate Gram-negative flora in varying levels (10(5)-10(7) cfu/g). The addition of nisin and/or a CO2-atmosphere increased the shelf-life to five or six weeks and limited the level of LAB to about 10(4)-10(6), 10(3)-10(6) and 10(2)-10(4) cfu/g, respectively. CO2-atmosphere +/- nisin inhibited the growth of Gram-negative bacteria, whereas nisin had no effect on these in vacuum packages. The Gram-negative flora on vacuum-packed salmon was dominated by a Vibrio sp., resembling V. marinus, Enterobacteriaceae (Enterobacter agglomerans, Serratia liquefaciens and Rahnella aquatilis) and occasionally Aeromonas hydrophila. Irrespective of the addition of nisin and/or CO2-atmosphere, the LAB microflora was dominated by Carnobacterium piscicola, which was found to account for 87% of the 255 LAB isolates characterized. Whole-cell-protein patterns analysed by SDS-PAGE confirmed the Carnobacterium species identification. The spoilage potential of C. piscicola isolates was further studied by inoculation of approx. 10(6) cfu/g in cold-smoked salmon stored at 5 degrees C. The salmon did not spoil within 4 weeks of storage in vacuum- or CO2-atmosphere, and it is concluded that despite high levels (> 10(7) cfu/g) of C. piscicola, sensory rejection was caused by autolytic changes. This was supported by the development of soft texture and sour, rancid and bitter off-flavours at the point of spoilage, irrespective of the length of shelf-life and low or high total counts of LAB and Gram-negative bacteria.


New species of the orb-weaving spider genus Chrysometa (Araneae, Tetragnathidae) from oak forests near of the Pico de Orizaba National Park (Veracruz, Mexico).
Seven new species of the genus Chrysometa Simon are described: C. citlaltepetl n. sp., C. triangulosa n. sp., C. rosarium n. sp., C. atotonilco n. sp., C. xamaticpac n. sp. C. puya n. sp. and C. sagicuta n. sp. Species identities were evaluated and sexes for each species matched with a fragment of the cytochrome c oxidase subunit I. These data were analyzed with maximum likelihood and the resulting cladograms separated all species with high support values (95-100) and an average distance of 0.093 %. The genetic signal also agreed with the diagnostic morphological features used to separate these taxa. The sex matching results discovered that the female of C. chipinque Levi actually belongs to C. puya n. sp.; the correct female of C. chipinque is here described for the first time. A redescription of the male of C. chipinque and the female of C. puya is also provided. All species were collected as part of a faunistic inventory from two oak forests near Pico de Orizaba Volcano National Park. A total of 399 adult specimens, 209 females and 195 males, were sorted and identified. Most individuals were collected from medium height vegetation by beating trays and from high vegetation by direct collecting at night. High resolution images for all species are available at www.unamfcaracnolab.com. Finally, the functional anatomy of the epigynum for the species described here is discussed.


Several Alphaherpesviruses Interact Similarly with the NF-κB Pathway and Suppress NF-κB-Dependent Gene Expression.
Alphaherpesvirus infection is associated with attenuation of different aspects of the host innate immune response that is elicited to confine primary infections at the mucosal epithelia. Here, we report that infection of epithelial cells with several alphaherpesviruses of different species, including herpes simplex virus 1 and 2 (HSV-1 and HSV-2), feline alphaherpesvirus 1 (FHV-1), and bovine alphaherpesvirus 1 (BoHV-1) results in the inactivation of the responses driven by the nuclear factor kappa B (NF-κB) pathway, considered a pillar of the innate immune response. The mode to interact with and circumvent NF-κB-driven responses in infected epithelial cells is seemingly conserved in human, feline, and porcine alphaherpesviruses, consisting of a persistent activation of the NF-κB cascade but a potent repression of NF-κB-dependent transcription activity, which relies on replication of viral genomes. However, BoHV-1 apparently deviates from the other investigated members of the taxon in this respect, as BoHV-1-infected epithelial cells do not display the persistent NF-κB activation observed for the other alphaherpesviruses. In conclusion, this study suggests that inhibition of NF-κB transcription activity is a strategy used by several alphaherpesviruses to prevent NF-κB-driven responses in infected epithelial cells. IMPORTANCE The current study provides a side-by-side comparison of the interaction of different alphaherpesviruses with NF-κB, a key and central player in the (proinflammatory) innate host response, in infected nontransformed epithelial cell lines. We report that all studied viruses prevent expression of the hallmark NF-κB-dependent gene IκB, often but not always via similar strategies, pointing to suppression of NF-κB-dependent host gene expression in infected epithelial cells as a common and therefore likely important aspect of alphaherpesviruses.


[Adsorption behavior of radioactive iodide and iodate in soil].
The adsorption behavior of radioiodine on soils has been studied. Soils were collected in Tokai, Ibaraki Pref . and classified with soil texture and contents of organic matter. Carrier-free radioiodine in iodide form is adsorbed on soil independent of soil properties, while radioiodine in iodate form is more readily adsorbed on soil which is abundant in organic, matter.


Two polysaccharides from Rehmannia glutinosa: isolation, structural characterization, and hypoglycemic activities.
Rehmannia glutinosa (RG) as a Chinese herbal medicine can be used both in medicine and food. As the main component of RG, the polysaccharides have a hypoglycemic effect, however, the hypoglycemic activity of RG homopolysaccharides remains unknown. We isolated and purified two polysaccharides, RGP70-1-1 and RGP70-1-2 (4.9 kDa and 2.8 kDa) from RG. The structural characteristics, including monosaccharide composition, linkage, and configuration were analyzed by FT-IR, HPLC, GC-MS, NMR spectroscopy, Congo test, and SEM. RGP70-1-1 and RGP70-1-2 consist of four monosaccharides (glucose, mannose, arabinose, and galactose). RGP70-1-1 contains 14 connection modes, with the linkages including l-Araf-(1→, →3)-l-Araf-(1→, →5)-l-Araf-(1→, →3,5)-l-Araf-(1→, →2,5)-l-Araf-(1→, d-Manp-(1→, →2)-d-Manp-(1→, →4)-d-Manp-(1→, d-Galp-(1→, →4)-d-Galp-(1→, →4,6)-d-Galp-(1→, →6)-d-Glcp-(1→, →4,6)-d-Glcp-(1→, →3,6)-d-Glcp-(1→. The linkages of RGP70-1-2 is including →5)-l-Araf-(1→, →3,5)-l-Araf-(1→, →4)-d-Manp-(1→, →3,6)-d-Manp-(1→, d-Galp-(1→, →6)-d-Galp-(1→, d-Glcp-(1→, →6)-d-Glcp-(1→, →4,6)-d-Glcp-(1→. Furthermore, RGP70-1-1 and RGP70-1-2 can inhibit α-glucosidase and α-amylase. RGP70-1-1 stimulated GLP-1 secretion in STC-1 cells and was related to the up-regulation of PI3K and p-AKT protein expression. The findings revealed a natural product with potential hypoglycemic activity, which may be used as a GLP-1 secretagogue and a beneficial functional food ingredient for T2D.


Electrothermally Tunable Graphene Resonators Operating at Very High Temperature up to 1200 K.
The unique negative thermal expansion coefficient and remarkable thermal stability of graphene make it an ideal candidate for nanoelectromechanical systems (NEMS) with electrothermal tuning. We report on the first experimental demonstration of electrothermally tuned single- and few-layer graphene NEMS resonators operating in the high frequency (HF) and very high frequency (VHF) bands. In single-, bi-, and trilayer (1L, 2L, and 3L) graphene resonators with carefully controlled Joule heating, we have demonstrated remarkably broad frequency tuning up to Δ f/ f0 ≈ 310%. Simultaneously, device temperature variations imposed by Joule heating are monitored using Raman spectroscopy; we find that the device temperature increases from 300 K up to 1200 K, which is the highest operating temperature known to date for electromechanical resonators. Using the measured frequency and temperature variations, we further extract both thermal expansion coefficients and thermal conductivities of these devices. Comparison with graphene electrostatic gate tuning indicates that electrothermal tuning is more efficient. The results clearly suggest that the unique negative thermal expansion coefficient of graphene and its excellent tolerance to very high temperature can be exploited for engineering highly tunable and robust graphene transducers for harsh and extreme environments.


Association between continued cannabis use during pregnancy and symptoms of anxiety and depression.
Cannabis use in pregnancy is common, as are mental health disorders, but the association between the two is not well established. This study is a single-site retrospective cohort. Urine testing for cannabis was evaluated at two-time points to categorize women as having never used, quit or continued to use. Edinburgh Postnatal Depression Scale (EPDS) and Generalized Anxiety Disorder (GAD) screen results were compared across groups using multinomial logistic regression. In addition, EPDS and GAD change scores between initiation of care and delivery were analyzed. 604 women were included, 221 (36.3%) with positive toxicology testing for cannabis at the initiation of care. Women who continued cannabis use were significantly more likely to have elevated GAD and EPDS scores (2.55 [1.31, 4.99]) and EPDS score (2.75 [1.43, 5.28]), respectively as compared to those with no use. No significant differences were found between groups in GAD or EPDS change scores t women with higher depression scores on the EPDS had 2.70 times the odds of being in the continuous use group compared to the quit using group (aOR = 2.70, 95% CI = [1.30, 5.88]). Both anxiety and depression symptoms were found to be associated with cannabis use and continued use during pregnancy.


Acute dyspnea caused by a giant spindle cell lipoma of the larynx.
The spindle cell lipoma (SCL) is a special type of lipoma and this is very rare in the head and neck regions. There are only five reported cases exist, which describes the occurrence of a SCL in the hypopharynx. Our case report presents a case of a very large SCL in the larynx. We want to describe that how we treated the patients and compared the situation with other reported cases. Intraoperatively, we found a tumor mass of 7 × 5 cm. It was successfully removed with the carbon dioxide laser. No postoperative complications occurred. Although SCL is a very rare diagnosis in the larynx/hypopharynx, it should be included in the differential diagnosis of larynx/hypopharynx tumors. Our case is the first report of such a large SCL in the larynx. The clinical symptoms occurred relatively late and ended up in an acute situation of stridor and dyspnea.


Hypomelanosis of Ito: a case report with clinical and ultrastructural data.
Hypomelanosis of Ito (HI) is an uncommon skin disorder characterized by the presence of hypochromic areas associated with visceral abnormalities, the most common being neurological, muscular, skeletal and ocular. The authors describe a typical case of hypomelanosis of Ito in a 7-year-old child. The patient was obese, suffered from scoliosis, flat feet and had a bilateral genu valgus. No neurological, ophthalmological or dental malformations were noted. An electron microscopic study of a hypomelanotic area showed decreased functional activity in the melanocytes, which contained only a few rudimentary cytoplasmatic projections and poorly developed organelles. In addition, there was a reduction in the number of mature melanosomes.


High Glucose Concentrations Affect Band 3 Protein in Human Erythrocytes.
Hyperglycemia is considered a threat for cell homeostasis, as it is associated to oxidative stress (OS). As erythrocytes are continuously exposed to OS, this study was conceived to verify the impact of either diabetic conditions attested to by glycated hemoglobin (Hb) levels (>6.5% or higher) or treatment with high glucose (15-35 mM, for 24 h) on erythrocyte homeostasis. To this aim, anion exchange capability through the Band 3 protein (B3p) was monitored by the rate constant for SO42- uptake. Thiobarbituric acid reactive species (TBARS), membrane sulfhydryl groups mostly belonging to B3p, glutathione reduced (GSH) levels, and B3p expression levels were also evaluated. The rate constant for SO42- uptake (0.063 ± 0.001 min-1, 16 min in healthy volunteers) was accelerated in erythrocytes from diabetic volunteers (0.113 ± 0.001 min-1, 9 min) and after exposure to high glucose (0.129 ± 0.001in-1, 7 min), but only in diabetic volunteers was there an increase in TBARS levels and oxidation of membrane sulfhydryl groups, and a decrease in both GSH and B3p expression levels was observed. A combined effect due to the glycated Hb and OS may explain what was observed in diabetic erythrocytes, while in in vitro hyperglycemia, early OS could explain B3p anion exchange capability alterations as proven by the use of melatonin. Finally, measurement of B3p anion exchange capability is a suitable tool to monitor the impact of hyperglycemia on erythrocytes homeostasis, being the first line of high glucose impact before Hb glycation. Melatonin may be useful to counteract hyperglycemia-induced OS at the B3p level.


Spiritual well-being and quality of life are impaired in chronic urticaria.
Background. Patients with chronic urticaria (CU) often report an impaired quality of life (QoL). Although a positive effect of addressing spirituality in health care has been proved in several chronic diseases, its potential role in CU has received no attention. Objective. We aim to evaluate spirituality and QoL in CU subjects. Methods. In a single-centre observational study, 100 CU subjects were investigated using Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, Chronic Urticaria Quality of life Questionnaire (CU-Q2oL) and Urticaria Control Test (UCT). Results. Of 100 subjects, 82 were female and 18 were male. It was observed that subjects with poorly controlled CU presented FACIT Sp-12 meaning/peace (p = 0.004) significantly lower, and CU-Q2oL (p less than 0.0001) significantly higher (worst QoL) than subjects with controlled CU. There was no difference in the FACIT Sp-12 faith (p = 0.43) between groups. There was moderate direct correlation between FACIT Sp-12 faith and FACIT Sp-12 meaning/peace (r = 0.483; p less than 0.0001; n = 100). There was a significant strong inverse correlation between the CU-Q2oL and the UCT (r = - 0.762; p less than 0.0001; n = 100). No correlation was found between the FACIT Sp-12 faith and CU-Q2oL, neither with UCT. Conclusions. No study has ever investigated the role of spirituality in managing patients with urticaria. Our findings support the impact of poorly controlled urticaria in spiritual well-being and QoL. Therefore, clinicians should pay more attention to spirituality among CU patients. We suggest that urticaria guidelines should include specific recommendations on spirituality assessment.


The dimensionality of language ability in school-age children.
This study asked if children's performance on language tests reflects different dimensions of language and if this dimensionality changes with development. Children were given standardized language batteries at kindergarten and at second, fourth, and eighth grades. A revised modified parallel analysis was used to determine the dimensionality of these items at each grade level. A confirmatory factor analysis was also performed on the subtest scores to evaluate alternate models of dimensionality. The revised modified parallel analysis revealed a single dimension across items with evidence of either test specific or language area specific minor dimensions at different ages. The confirmatory factor analysis tested models involving modality (receptive or expressive) and domain (vocabulary or sentence use) against a single-dimension model. The 2-dimensional model involving domains of vocabulary and sentence use fit the data better than the single-dimensional model; however, the single-dimension model also fit the data well in the lower grades. Much of the variance in standardized measures of language appears to be attributable to a single common factor or trait. There is a developmental trend during middle childhood for grammatical abilities and vocabulary abilities to become differentiated. These measures do not provide differential information concerning receptive and expressive abilities.


[Treatment failure due to acquisition of antibiotic resistance: report of two clinical cases].
We describe two cases of treatment failure due to intra-treatment acquisition of antibiotic resistant microorganisms with the aim of highlighting the possible molecular mechanisms by which treatment failure occurred. We analyzed the clinical histories and the isolates obtained from 2 patients, one with a urinary tract infection (UTI) by E. coli, initially treated with cefuroxim (to which the isolate was susceptible), and another with osteoarthritis (OA) treated initially with meropenem plus vancomycin, developing K. pneumoniae susceptible to meropenem. During treatment, in both patients, resistant microorganisms were isolated, and empirical therapy was modified, initially with ceftriaxone and afterwards meropenem in case 1, and adding amikacin in case 2. Both strains (per patient) were compared by PFGE and resistance genes were sought by PCR. Regarding the UTI, the initial strain acquired an IncFIB SHV-5-producing plasmid. In the OA case, the initial susceptible strain was substituted by a CTX-M-9 and AadB-AadA2-Aac(6')Ib-producing K. pneumoniae.


Proteohistography--direct analysis of tissue with high sensitivity and high spatial resolution using ProteinChip technology.
On the proteomic level, all tissues, tissue constituents, or even single cells are heterogeneous, but the biological relevance of this cannot be adequately investigated with any currently available technique. The analysis of proteins of small tissue areas by any proteomic approach is limited by the number of required cells. Increasing the number of cells only serves to lower the spatial resolution of expressed proteins. To enhance sensitivity and spatial resolution we developed Proteohistography. Laser microdissection was used to mark special areas of interest on tissue sections attached to glass slides. These areas were positioned under microscopic control directly on an affinity chromatographic ProteinChip Array so that cells were lysed and their released proteins bound on a spatially defined point. The ProteinChip System, surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS), allows the laser to be steered to up to 215 distinct positions across the surface of the spot, enabling a high spatial resolution of measured protein profiles for the analyzed tissue area. Protein profiles of the single positions were visually plotted over the used tissue section to visualize distribution proteohistologically. Results show that the spatial distribution of detectable proteins could be used as a Proteohistogram for a given tissue area. Consequently, this procedure can provide additional information to both a matrix-assisted laser desorption/ionization (MALDI)-based approach and immunohistochemistry, as it is more sensitive, highly quantitative, and no specific antibody is needed. Hence, proteomic heterogeneity can be visualized even if proteins are not known or identified.


Aims and approaches of Web-RADR: a consortium ensuring reliable ADR reporting via mobile devices and new insights from social media.
Advent of new technologies in mobile devices and software applications is leading to an evolving change in the extent, geographies and modes for use of internet. Today, it is used not only for information gathering but for sharing of experiences, opinions and suggestions. Web-Recognizing Adverse Drug Reactions (RADR) is a groundbreaking European Union (EU) Innovative Medicines Innovation funded 3-year initiative to recommend policies, frameworks, tools and methodologies by leveraging these new developments to get new insights in drug safety. Data were gathered from prior surveys, previous initiatives and a review of relevant literature was done. New technologies provide an opportunity in the way safety information is collected, helping generate new knowledge for safety profile of drugs as well as unique insights into the evolving pharmacovigilance system in general. It is critical that these capabilities are harnessed in a way that is ethical, compliant with regulations, respecting data privacy and used responsibly. At the same time, the process for managing and interpreting this new information must be efficient and effective for sustenance, thoughtful use of resources and valuable return of knowledge. These approaches should complement the ongoing progress toward personalized medicine. This Web-RADR initiative should provide some directions on 'what and how' to use social media to further proactive pharmacovigilance and protection of public health. It is expected to also show how a multipronged expert consortium group comprising regulators, industry and academia can leverage new developments in technology and society to bring innovation in process, operations, organization and scientific approaches across its boundaries and beyond the normal realms of individual research units. These new approaches should bring insights faster, earlier, specific, actionable and moving toward the target of AE prevention. The possibilities of a blended targeted pharmacovigilance (PV) approach where boundaries between stakeholders blur and cultures mix point to very different future for better, healthier and longer lives.


The "hidden ligand" of the galactose-binding protein.
Following tryptophan fluorescence of the galactose-binding during dissociation of the ligand it has been found that glucose dissociates with a half life of less than 5 s. Similarly, fast dissociation was also observed by following release of radioactively labelled glucose from Sepharose-coupled galactose-binding protein upon dilution. Accordingly, a previous claim that the galactose-binding protein contains glucose as a non-dissociable "hidden ligand" [G. Richarme and A. Kepes (1974) Eur. J. Biochem. 45, 127-133] has to be reinterpreted


Time resolved quantitative imaging of charring in materials at temperatures above 1000 K.
A device is presented allowing for in situ investigation of chemically changing materials by means of X-ray imaging. A representative cork ablator sample, additionally instrumented with thermocouples, is encapsulated in an evacuated cell heating a sample surface with a heat flux of 230 kW/m(2). The images show the sample surface and the in-depth progression of the char front dividing the char layer from the virgin material. Correlating the images to thermocouple data allows for the deduction of a reaction temperature. For the representative cork ablator investigated at the present conditions, the progression rate of the pyrolysis layer is determined to 0.0285 mm/s and pyrolysis temperature is 770 or 737 K, depending on the pre-existing conditions. It is found that the novel device is ideally suited for volume process imaging.


Formation of a vitamin C conjugate of acrolein and its paraoxonase-mediated conversion into 5,6,7,8-tetrahydroxy-4-oxooctanal.
Vitamin C (ascorbic acid) has been reported to participate in Michael addition reactions in vitro to form vitamin C conjugates with alpha,beta-unsaturated aldehydes, such as acrolein. This study shows evidence for the formation and metabolism of the vitamin C conjugate of acrolein (AscACR) in cultured human monocytic THP-1 cells exposed to acrolein diacetate. By using (18)O and (13)C labeling in combination with liquid chromatography-tandem mass spectrometry, AscACR was shown to undergo hydrolytic conversion of the ascorbyl lactone into an intermediate carboxylic acid. Subsequent decarboxylation of the carboxylic acid yielded 5,6,7,8-tetrahydroxy-4-oxooctanal (THO). When THP-1 cells were pretreated with ascorbic acid (1 mM, 18 h) and then exposed to acrolein diacetate, THO was detected as its pentafluorobenzyl oxime derivative in the cell lysates and medium. Treatment of THP-1 cells with both ascorbic acid and acrolein diacetate was required for THO formation. The formation of THO from AscACR was facilitated by the lactonase enzymes, human recombinant paraoxonases 1 and 2. THP-1 cells exhibited PON activity, which explains the catalytic conversion of AscACR into THO in these cells. THO was formed in addition to metabolites of the glutathione conjugate of acrolein, indicating that THO formation contributes to the elimination of acrolein in a cellular environment.


The cellular prion protein traps Alzheimer's Aβ in an oligomeric form and disassembles amyloid fibers.
There is now strong evidence to show that the presence of the cellular prion protein (PrP(C)) mediates amyloid-β (Aβ) neurotoxicity in Alzheimer's disease (AD). Here, we probe the molecular details of the interaction between PrP(C) and Aβ and discover that substoichiometric amounts of PrP(C), as little as 1/20, relative to Aβ will strongly inhibit amyloid fibril formation. This effect is specific to the unstructured N-terminal domain of PrP(C). Electron microscopy indicates PrP(C) is able to trap Aβ in an oligomeric form. Unlike fibers, this oligomeric Aβ contains antiparallel β sheet and binds to a oligomer specific conformational antibody. Our NMR studies show that a specific region of PrP(C), notably residues 95-113, binds to Aβ oligomers, but only once Aβ misfolds. The ability of PrP(C) to trap and concentrate Aβ in an oligomeric form and disassemble mature fibers suggests a mechanism by which PrP(C) might confer Aβ toxicity in AD, as oligomers are thought to be the toxic form of Aβ. Identification of a specific recognition site on PrP(C) that traps Aβ in an oligomeric form is potentially a therapeutic target for the treatment of Alzheimer's disease.


The Effects of Attractiveness and Source Expertise on Online Health Sites.
The surface characteristics (presentational or design elements) of online content have been the focus of a growing body of credibility literature in recent decades. However, since the online health information communities such as WebMD do not provide any design options when writing comments on the original post, how the simplistic presentational of comments (e.g., spacing, bullet-points, labeling, and line breaks) can affect web users' responses was examined. Our study found that minimal variations in the presentation of online contents can influence assessments of their credibility and behavioral intentions. In addition, the current study revealed interaction effects between surface characteristics and source expertise. Other findings and implications are discussed.


Bilateral Atrial Myxoma: A Case Report.
Among the rare cardiac tumors, myxoma, which is mostly located in the left atrium, is the most common type. Bilateral atrial myxoma is extremely rare, and requires urgent surgery. The authors report the case of a 34-year-old male, who presented with one month of right hemiparesis and aphasia and subsequently diagnosed with bilateral atrial myxoma based on transthoracic echocardiography. An urgent operation for intra-cardiac tumor removal was performed with the biatrial approach. Once a diagnosis of myxoma has been made, an urgent operation for tumor removal is necessary due to the risk of serious complications, including sudden death from normal blood flow obstruction.


Klotho and the Treatment of Human Malignancies.
Klotho was first discovered as an anti-ageing protein linked to a number of age-related disease processes, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions. Emerging research has also demonstrated a potential therapeutic role for Klotho in cancer biology, which is perhaps unsurprising given that cancer and ageing share similar molecular hallmarks. In addition to functioning as a tumour suppressor in numerous solid tumours and haematological malignancies, Klotho represents a candidate therapeutic target for patients with these diseases, the majority of whom have limited treatment options. Here, we examine contemporary evidence evaluating the anti-neoplastic effects of Klotho and describe the modulation of downstream oncogenic signalling pathways, including Wnt/β-catenin, FGF, IGF1, PIK3K/AKT, TGFβ, and the Unfolded Protein Response. We also discuss possible approaches to developing therapeutic Klotho and consider technological advances that may facilitate the delivery of Klotho through gene therapy.


Improvement of Green Upconversion Monochromaticity by Doping Eu3+ in Lu2O3:Yb3+/Ho3+ Powders with Detailed Investigation of the Energy Transfer Mechanism.
The monochromaticity improvement of green upconversion (UC) in Lu2O3:Yb3+/Ho3+ powders has been successfully realized by tridoping Eu3+. The integral area ratio of green emission to red emission of Ho3+ increases 4.3 times with increasing Eu3+ doping concentration from 0 to 20 mol %. The energy transfer (ET) mechanism in the Yb3+/Ho3+/Eu3+ tridoping system has been investigated carefully by visible and near-infrared (NIR) emission spectra along with the decay curves, revealing the existence of ET from the Ho3+5F4/5S2 level tothe Eu3+5D0 level and ET from the Ho3+5I6 level to the Eu3+7F6 level. In addition, the population routes of the red-emitting Ho3+5F5 level in the Yb3+/Ho3+ codoped system under 980 nm wavelength excitation have also been explored. The ET process from the Yb3+2F5/2 level to the Ho3+5I7 level and the cross-relaxation process between two nearby Ho3+ ions in the 5F4/5S2 level and 5I7 level, respectively, have been demonstrated to be the dominant approaches for populating the Ho3+5F5 level. The multiphonon relaxation process originating from the Ho3+5F4/5S2 level is useless to populate the Ho3+5F5 level. As the energy level gap between the Ho3+5I7 level and Ho3+5I8 level matches well with that between Eu3+7F6 level and Eu3+7F0 level, the energy of the Ho3+5I7 level can be easily transferred to the Eu3+7F6 level by an approximate resonant ET process, resulting in a serious decrease in the red UC emission intensity. Since this ET process is more efficient than the ET from the Ho3+5F4/5S2 level to the Eu3+5D0 level as well as the ET from the Ho3+5I6 level to the Eu3+7F6 level, the integral area ratio of green emission to red emission of Ho3+ has been improved significantly.


Direct imaging of domains in the Lbeta' state of 1,2-dipalmitoylphosphatidylcholine bilayers.
A near-field scanning optical microscope was used to study domain formation and evolution in single-component supported lipid bilayers in the gel (L(beta') state. Results on 1,2-dipalmitoylphosphatidylcholine (DPPC) bilayers on glass substrates at room temperature are presented. The domain structure is determined by means of the optical anisotropy of the sample, which arises because DPPC molecules are tilted at theta approximately 32 degrees with respect to the bilayer normal [J. F. Nagle and S. Tristram-Nagle, Biochim. Biophys. Acta 1469, 159 (2000)]. From the measurements we obtain the difference in the index of refraction for the directions parallel and perpendicular to the acyl chains of the lipid molecules, Delta(n)=0.37+/-0.12, in good agreement with calculated and measured values. Direct evidence of the existence of domains in the L(beta') state is provided. These domains, defined as the correlation of the tilt angle theta, are found to be 1-2 microm across. Furthermore, it was found that they are robust under single-lipid-molecule diffusion, remaining unchanged over periods of hundreds of minutes.


Relationship of child perceptions of maternal pain to children's laboratory and non-laboratory pain.
Previous research has established links between parent and child pain. However, little is known about sex-specific parent-child pain relationships in a nonclinical population. A sample of 186 children aged eight to 18 years (49% female) provided information on maternal and self bodily pain, assessed by asking children about the presence and location of bodily pain experienced. Children also completed three laboratory pain tasks and reported on cold pressor pain intensity, pressure pain intensity and heat pain intensity. The presence of child-reported maternal pain was consistently correlated with daughters' bodily and laboratory pain, but not with sons' pain in bivariate analyses. Multivariate analyses controlling for child age and maternal psychological distress indicated that children of mothers with bodily pain reported more total bodily pain sites as well as greater pressure and cold pain intensity, relative to children of mothers without bodily pain. For cold pain intensity, these results differed for boys versus girls, in that daughters reporting maternal pain evidenced significantly higher cold pain intensity compared with daughters not reporting maternal pain. No such differences were found for boys. The findings suggest that children's perceptions of maternal pain may play a role in influencing children's own experience of pain, and that maternal pain models may affect boys and girls differently.


The evolution of beta-cell dysfunction and insulin resistance in type 2 diabetes.
Insulin resistance and beta-cell dysfunction have important roles in the pathogenesis and evolution of type 2 diabetes. The development of precise methods to measure these factors has helped us to define the relationship between them and evidence is reviewed that changes in insulin sensitivity are compensated by inverse changes in beta-cell responsiveness such that the product of insulin sensitivity and insulin secretion (the disposition index) remains constant. While the disposition index promises to be a useful tool to predict individuals at high risk of developing type 2 diabetes, other factors that contribute to beta-cell dysfunction and mark disease onset and progression include impairments in proinsulin processing and insulin secretion, decreased beta-cell mass and islet amyloid deposition. Emerging data indicate that anti-diabetic agents, such as the thiazolidinediones that simultaneously target insulin resistance and beta-cell dysfunction, may have a beneficial impact on disease onset and progression. Several landmark clinical studies are underway to investigate if their initial promise is supported by data from large-scale trials.


Light-triggered multi-joint microactuator fabricated by two-in-one femtosecond laser writing.
Inspired by the flexible joints of humans, actuators containing soft joints have been developed for various applications, including soft grippers, artificial muscles, and wearable devices. However, integrating multiple microjoints into soft robots at the micrometer scale to achieve multi-deformation modalities remains challenging. Here, we propose a two-in-one femtosecond laser writing strategy to fabricate microjoints composed of hydrogel and metal nanoparticles, and develop multi-joint microactuators with multi-deformation modalities (>10), requiring short response time (30 ms) and low actuation power (<10 mW) to achieve deformation. Besides, independent joint deformation control and linkage of multi-joint deformation, including co-planar and spatial linkage, enables the microactuator to reconstruct a variety of complex human-like modalities. Finally, as a proof of concept, the collection of multiple microcargos at different locations is achieved by a double-joint micro robotic arm. Our microactuators with multiple modalities will bring many potential application opportunities in microcargo collection, microfluid operation, and cell manipulation.


Antitumour effect of valproic acid against salivary gland cancer in vitro and in vivo.
Salivary gland cancer (SGC) has a comparatively poor prognosis and is prone to frequent recurrence and metastases. Therefore, the development of more effective chemotherapy against SGC is desirable. The aim of the present study was to investigate the antitumour effects of valproic acid (VPA) against SGC in vitro and in vivo. Two human SGC cell lines (HSY and HSG cells) were used in the present study. The effects of VPA on the proliferation of SGC cells in vitro were assessed by MTT assay. Cancer cells treated with VPA were subjected to cell cycle analysis by flow cytometry. In addition, the expression levels of p21 and p27 were examined by real-time RT-PCR to identify the mechanisms of the antitumour effect of VPA on SGC. The effects of VPA on cancer growth in vivo were evaluated in a xenograft model. VPA inhibited the proliferation of SGC cells in a dose-dependent manner in vitro. Degenerated cancer cells were observed at high concentrations of VPA. In the cell cycle analysis, VPA induced cell-growth inhibition and G1 arrest of cell cycle progression in both cancer cell lines in a time- and dose-dependent manner. VPA markedly upregulated the mRNA expression levels of both p21 and p27 in both SGC cell lines in a time-dependent manner. In the xenograft model experiment, VPA treatment markedly inhibited the growth of salivary gland tumours when compared with the growth of the untreated controls. VPA may be a valuable drug in the development of better therapeutic regimens for SGC.


Remembering is in the details: effects of test-list context on memory for an event.
We examined how recognition judgements for a set of event details are influenced by the relative difficulty of the other details included on the test. Participants viewed a crime event and then assigned remember/know judgements to details on a recognition test. In Experiment 1, details of medium difficulty were more likely to be classified as remembered when mixed with hard details rather than easy details. Similarly, in Experiment 2, medium details presented in blocked format were more likely to be classified as remembered when preceded by a block of hard details rather than a block of easy details. The test-list context thus appears to influence how participants define remembering. In Experiment 3, informing participants of the relative difficulty of the upcoming block of details eliminated the blocking effect. Implications for accounts of remember/know judgements and for conducting memory interviews are discussed.


Sociodemographic characteristics associated with binge drinking among Brazilians.
Binge drinking (BD) is a harmful pattern of alcohol use. This study describes this pattern of drinking and the sociodemographic variables associated with it in a representative sample of Brazilians. A cross-sectional survey of 3007 individuals using a multistage probabilistic sample was conducted in 143 Brazilian municipalities. The frequency of BD in the year preceding the study was assessed. BD was defined as the consumption of four drinks of alcohol within a two-hour period for women and five drinks in two hours for men. Weighted-ordered logit regression was used to assess the relationship between sociodemographic factors and BD. Most respondents had not engaged in binge drinking (69.7%; 95% confidence interval (CI) 67.0-72.2%). Binge drinking was more common among participants who were male (odds ratio (OR) 2.9; 95% CI 2.3-3.6) or single (OR 1.5; 95% CI 1.1-2.1) or had higher family income (OR 2.3; 95% CI 1.3-3.8). Individuals between 18 and 44 years of age were four times more likely to engage in binge drinking than adolescents (OR 4.7; 95% CI 3.3-6.8). Evangelicals/Protestants were less likely to engage in binge drinking (OR 0.7; 95% CI 0.2-0.5). Our study, which is the first representative survey of BD in Brazil, showed that the age range of adults who engaged in BD is wider than the age range observed in other countries. These individuals are at increased risk for the adverse consequences of binge drinking, including addiction, car accidents, involvement in crime, absenteeism, and family violence.


[Effects of Oral Gargling with Aroma Solution in Psychiatric Inpatients: A Non-Randomized Controlled Trial].
The purpose of this study was to examine the effects of oral gargling with an aromatic solution on xerostomia, objective oral status, and oral health-related quality of life in psychiatric inpatients. A nonequivalent control group with a non-synchronized design was used in this study. The experimental group (n=34) received oral gargling with an aroma solution, while the control group (n=33) gargled with 0.9% normal saline. Dependent variables were measured at pre-, post-, and follow-up test. Data were analyzed using an χ²-test, Fisher's exact probability test, t-tests, and repeated measures ANOVA using SPSS/WIN v.21.0. After the intervention, significant differences were revealed in xerostomia (F=15.30, p <.001), objective oral status (F=38.44, p <.001), and oral health-related quality of life (F=62.70, p <.001) with an interaction effect between group and time. These findings indicate that gargling with an aroma solution is more effective than 0.9% normal saline for the oral health of psychiatric inpatients. Therefore gargling with an aroma can be safely recommended as a brief, economical, and positive intervention in clinical settings.


The impact of micronized progesterone on breast cancer risk: a systematic review.
Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. The debate on bioidentical hormones including micronized progesterone has increased in recent years. Based on a systematic literature review on the impact of menopausal hormone therapy (MHT) containing micronized progesterone on the mammary gland, an international expert panel's recommendations are as follows: (1) estrogens combined with oral (approved) or vaginal (off-label use) micronized progesterone do not increase breast cancer risk for up to 5 years of treatment duration; (2) there is limited evidence that estrogens combined with oral micronized progesterone applied for more than 5 years are associated with an increased breast cancer risk; and (3) counseling on combined MHT should cover breast cancer risk - regardless of the progestogen chosen. Yet, women should also be counseled on other modifiable and non-modifiable breast cancer risk factors in order to balance the impact of combined MHT on the breast.


The educational experiments of school health promotion for the youth in Japan: analysis of the 'sport test' over the past 34 years.
The objective of this study was to analyze independently the results of a 'sport test' that had been conducted in Japanese schools for 34 years without interruption, and to examine how physical education in Japanese schools affects health promotion in youths and what problems remain to be solved. The source of materials for the present study were the Annual Reports on the Survey of Physical Fitness and Athletic Ability for the period 1965-1998, published by the Ministry of Education, Science, Sports and Culture. Means and standard deviations of total scores from physical fitness and athletic ability tests in 11-year-olds (6th graders in elementary school), 14-year-olds (3rd graders in junior high school) and 17-year-olds (3rd graders in senior high school) were analyzed. The results of this study suggest that the trends of changes in mean score and coefficient of variation (CV) for physical fitness and athletic ability in Japanese youths are associated with the outcome of physical training through physical education in school, as well as the effect of the media--mainly television and television games. (1) The increase in mean scores and the decrease in CV observed from 1964 to the first half of the 1970s were probably due to the positive influence of the Guideline for Teaching. This guideline emphasized a systematic approach to athletic techniques, together with active practice of physical fitness training in schools, under the directives of the Boards of Education in response to the social 'Physical Fitness Campaign' policy at that time. (2) The leveling off of mean scores and CVs observed from the early half of the 1970s to the later half of the 1980s might be a result of the invasion of television into Japanese family life. (3) The decrease in mean scores and increase in CV observed since the later half of the 1980s were assumed to be caused by the negative influence of a Guideline for Teaching characterized by the key words 'Physical Education for More Pleasure' and a steep increase in the number of television games. (4) In terms of methodology, analyzing not only the mean scores but also the CV probably provided a more accurate evaluation of the outcome of health promotion in youths. In conclusion, strategies for health promotion in youths, especially for proper nurturing of physical fitness and athletic ability, should include not only delivery of physical fitness training in schools, but also continuous monitoring of multiple indicators, and ensuring proper 'Learning of the Body'. The latter should include providing learning opportunities centering on the 'body' (not the 'body' for the sake of labour or military manpower, but one's own 'body' per se); guiding young people to recognize the states of their own body and physical fitness, and to understand how they can be improved. To be effective in implementation, the need to increase the number of professional teachers in physical education should be examined. All possible opportunities should also be taken to inform youths of the negative effects of television and television games, and to encourage them to spend less time on these and more time being physically active from the moment they arise.


Viral manipulation of STAT3: Evade, exploit, and injure.
Signal transducer and activator of transcription 3 (STAT3) is a key regulator of numerous physiological functions, including the immune response. As pathogens elicit an acute phase response with concerted activation of STAT3, they are confronted with two evolutionary options: either curtail it or employ it. This has important consequences for the host, since abnormal STAT3 function is associated with cancer development and other diseases. This review provides a comprehensive outline of how human viruses cope with STAT3-mediated inflammation and how this affects the host. Finally, we discuss STAT3 as a potential target for antiviral therapy.


Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases.
Hyperlipidemia causes systemic lipid disorder, which leads to hepatic steatosis and atherosclerosis. Thus, it is necessary to detect these syndromes early and precisely to improve prognosis. In the affected regions, abnormal formation and growth of lipid droplets is observed; therefore, lipid droplets may be a suitable target for the diagnosis of hyperlipidemia-related syndromes. In this study, we designed and synthesized [99mTc]Tc-BOD and [99mTc]Tc-MBOD composed of one technetium-99m and two BODIPY scaffolds with hydroxamamide (Ham) or N-methylated hydroxamamide (MHam) in radiochemical yields of 54 and 35%, respectively, with a radiochemical purity of over 95%. [99mTc]Tc-BOD showed significantly higher accumulation levels in foam cells than in non-foam cells (foam cells: 213.8 ± 64.8, non-foam cell: 126.2 ± 26.9 %dose/mg protein, p < 0.05) 2 h after incubation. In contrast, [99mTc]Tc-MBOD showed similar accumulation levels in foam cells and non-foam cells (foam cells: 92.2 ± 23.3, non-foam cell: 83.8 ± 19.8 %dose/mg protein). In normal mice, [99mTc]Tc-BOD exhibited gradual blood clearance (0.5 h: 4.98 ± 0.35, 6 h: 1.94 ± 0.12 %ID/g) and relatively high accumulation in the liver 6 h after administration (15.22 ± 1.72 %ID/g). Therefore, [99mTc]Tc-BOD may have potential as an imaging probe for detecting lipid droplets in disease lesions of hyperlipidemia.


Self-efficacy mediates the effects of topiramate and GRIK1 genotype on drinking.
Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (1) altered the association between daily self-efficacy and later-day drinking; and (2) had an indirect effect on drinking via self-efficacy. In a 12-week, placebo-controlled trial of topiramate, we used daily interactive voice response technology to measure self-efficacy (i.e. confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European-American heavy drinkers. Topiramate's effects on both self-efficacy and drinking level were moderated by rs2832407. C-allele homozygotes treated with topiramate showed higher levels of self-efficacy and lower levels of nighttime drinking across the 12-week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self-efficacy. By modeling topiramate's effects on nighttime drinking across multiple levels of analysis, we found that self-efficacy, a key psychologic construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e. genotype) to select treatment to optimize the reduction in heavy drinking and thereby provide a personalized treatment approach.


Maternal thyroid parameters in pregnant women with different ethnic backgrounds: Do ethnicity-specific reference ranges improve the diagnosis of subclinical hypothyroidism?
Guidelines on the management of thyroid dysfunction during pregnancy have recently been updated and, for the diagnosis of subclinical hypothyroidism (SCH), a thyroid-stimulating hormone (TSH) upper reference limit (cut-off) of 4.0 mIU/L has been proposed when no institutional values are available. It is also suggested that serum TSH and thyroid autoimmunity (TAI) may be different according to the ethnic background of the women. We therefore determined the prevalence of TAI and SCH in pregnant women with different ethnic backgrounds and, to define SCH, we used different first trimester TSH upper reference cut-offs (institutional, ethnicity-specific, 2.5 mIU/L [Endocrine Society] and 4.0 mIU/L [American Thyroid Association]). Cross-sectional data analysis of 1683 pregnant women nested within an ongoing prospective database of pregnant women. The study was performed in a single centre in Brussels, Belgium. During the first antenatal visit, thyroid peroxidase antibodies (TPO-abs), TSH and free T4 (FT4) were measured and baseline characteristics recorded. Data from 481 women with sub-Saharan (SaBg; 28.6%), 754 North African (NaBg; 44.8%) and 448 Caucasian (CaBg; 26.6%) backgrounds were analysed. For the calculation of TSH reference ranges, women with TAI, outliers, twin and assisted pregnancies were excluded. The prevalence of TAI was significantly lower in the SaBg group than in NaBg and CaBg groups (3.3% vs 8.6% and 11.1%; P<.001, respectively). Median TSH was significantly lower in SaBg and NaBg groups as compared with the CaBg group (1.3 and 1.4 vs 1.5 mIU/L; P=.006 and .014, respectively). The prevalence of women with SCH was comparable between all groups when 2.5 mIU/L was used as cut-off, but when 4.0 mIU/L or the institutional cut-off (3.74 mIU/L) was used, it was significantly higher in the CaBg group vs the NaBg group (5.4% vs 2.1% and 7.1% vs 3.3%, P=.008 and .013, respectively). The use of ethnicity-specific cut-offs did not change the prevalence of SCH as compared to the use of institutional cut-offs. However, when these cut-offs were used, the prevalence of SCH reduced by >70% (4.5% instead of 16.7%; P<.001) relative to the 2.5 mIU/L cut-off. Pregnant women with a sub-Saharan African background had a lower prevalence of TAI and TSH levels as compared with women from other backgrounds. The use of ethnicity-specific TSH cut-offs in early pregnancy was not more specific for the diagnosis of SCH as compared to the use of the institutional cut-off.


Spectrally matched duplexed nucleic acid bioassay using two-colors from a single form of upconversion nanoparticle.
Optical sensing can provide opportunity for simultaneous determination of multiple targets as well as for implementation of ratiometric methods that can improve accuracy and precision. Herein we report a paper-based two-color oligonucleotide detection assay with tunable sensitivity that is based on use of a single type of upconversion nanoparticle (UCNP). Water-soluble UCNPs were designed to concurrently offer green and red emission. These avidin functionalized UCNPs were adsorbed onto a cellulose support, and Cy3 was used as a green channel acceptor for Survival Motor Neuron (SMN1) target, and Cy5.5 was the red channel acceptor for the glucuronidase gene (uidA) target. Selective DNA hybridization of the labeled targets with the corresponding probe provided emission from dyes, which was the basis for concurrent quantification of both targets. The limit of detection (LOD) could be tuned by changing the relative ratio of the SMN1 and uidA probes. A higher proportion of a probe provided for a lower LOD. When the SMN1/uidA probe ratio was 1:4, the LOD for SMN1 and uidA target were 54.3 and 30.5 fmol, and when the probe ratio was 4:1, the LOD for the above targets were 22.1 and 1260 fmol, respectively. Selectivity evaluation showed that one base pair mismatched DNA for SMN1 and uidA could be discriminated in most cases. The assay showed resistance to nonspecific adsorption of interfering DNA and protein and was even functional for targets in undiluted serum. This work represents a significant step in the development of paper-based multiplexed UCNP luminescence assays.


Microspectrophotometric studies of Romanowsky stained blood cells. I. Subtraction analysis of a standardized procedure.
This paper describes a microspectrophotometric study of blood smears stained by a simple, standardized Romanowsky technique, using only the dyes azure B and cosin. Absorbance spectra are presented for twenty-two classes of cellular object, and for the two dyes in solution, together with tabulations of spectral maxima, and suitable wavelengths for use in automated image processing. The colours of objects stained with azure B/eosin are discussed in terms of absorbance spectra. By a spectral subtraction technique, it is shown that the differential colouration of various cell structures may be explained satisfactorily in terms of the varying proportions of only four dye components. These are the monomers and dimers of azure B and eosin. Polymerization was found to occur both in solution and on binding to biopolymers. A similar analysis of a conventional Romanowsky stain would present much greater difficulties, due to the greater number of dye components, which, however, contribute little to the colours observed.


Editorial of Special Issue "New Aspects of the Hepatocyte Growth Factor/c-Met System".
HGF/c-Met system has covered, in the past two decades, multiple areas of research, from basic cell biology to clinical trials. This research topic witnessed a good deal of scientific interest and progress. [...].


Bayesian Tomography for Projections with an Arbitrary Transmission Function with an Application in Electron Microscopy.
The vast majority of the developments in tomography assume that the transmission of the probe through the sample follows Beer's Law, i.e., the rule of exponential attenuation. However, for transmission electron microscopy of samples a few times their mean free path, Beer's Law is no longer an accurate description of the transmission of the probe as a function of the sample thickness. Recent simulations [Z. H. Levine, Appl. Phys. Lett. 82, 3943 (2003)] have demonstrated accounting for the correct transmission function leads to superior tomographic reconstructions for a photonic band gap sample 8 µm square. Those recent simulations assumed that data was available at all angles, i.e., over 180°. Here, we consider a limited-angle case by generalizing the Bayesian formalism of Bouman and Sauer to allow an arbitrary transmission function. The new formalism is identical to that of Bouman and Sauer when the transmission function obeys Beer's Law. The examples, based on 140° of data, suggest that using the physical transmission function is a requirement for performing limited angle reconstructions.


Routine rectal retroflexion during colonoscopy has a low yield for neoplasia.
To investigate the value of retroflexion in detecting neoplasia in the distal rectum. This was a prospective observational study performed in an academic endoscopy unit. Consecutive patients undergoing colonoscopy had careful forward viewing of the distal rectum by retroflexion. Of 1502 procedures, 1076 (72%) procedures were performed with a 140 degrees angle of view colonoscope and 426 (28%) were performed with a 170 degrees angle of view colonoscope. The outcome measurement was the yield of neoplasia in the distal rectum detected by forward viewing vs retroflexion. A total of 1502 patients, including 767 (51%) females and 735 (49%) males, with mean age of 58.8 +/- 12.5 years were enrolled. Retroflexion was successful in 1411 (93.9%) patients, unsuccessful or not performed because the rectum appeared narrow in 91 (6.1%). Forty patients had a polyp detected in the distal rectal mucosa. Thirty-three were visible in both the forward and retroflexed view (25 hyperplastic, 8 adenomatous). Seven polyps were visualized only by retroflexion (6 hyperplastic sessile polyps, one 4 mm sessile tubular adenoma). There was no significant difference in information added by retroflexion with 140 degrees vs 170 degrees angle of view instrument. To our knowledge, this is the largest reported evaluation of retroflexion in the rectum. Routine rectal retroflexion did not detect clinically important neoplasia after a careful forward examination of the rectum to the dentate line. Since retroflexion has risks and may cause discomfort, the use of routine retroflexion should be at the discretion of the endoscopist.


Reviewing the Nutrition and Health Claims Regulation (EC) No. 1924/2006: What do we know about its challenges and potential impact on innovation?
Health claims potentially represent an opportunity for firms to engage in product differentiation and thereby induce investment into R&D and innovation in the food sector. The Nutrition and Health Claims Regulation (EC) No. 1924/2006 (NHCR) aims at protecting and promoting innovation as one of its objectives. However, existing studies indicate that this regulation may create several challenges for innovation in the food sector. To this end, we review the challenges related to the NHCR (Article 13.1) and its impact on innovation. Extant literature suggests that companies face challenges related to changing list of ingredients, missing transparency, wording of claims, limited financial resources, limited R&D resources, switching product categories and abandoning the functional foods sector. Moreover, current studies imply that so far the NHCR (in specific Article 13.1) does not seem to encourage innovation in the EU food sector.


Direct synthesis of novel quinoxaline derivatives via palladium-catalyzed reductive annulation of catechols and nitroarylamines.
Here, a palladium-catalyzed new hydrogenative annulation reaction of catechols and nitroarylamines, allowing straightforward access to two classes of novel quinoxaline derivatives, is reported. The reaction proceeds with operational simplicity, an easily available catalyst system, and a broad substrate scope, and without the need for pre-functionalization, which offers the potential for further design of new reductive transformations of renewable resources into value-added products.


Chronic drinking, binge drinking, and drunk driving II.
Data from the Rhode Island Behavioral Risk Factor Survey on self-reported alcohol consumption and drunk driving were examined. Driving while intoxicated was significantly associated with both binge drinking and chronic drinking, but the measures of drinking were not significantly associated.