The pathogenesis of H3N8 canine influenza virus in chickens, turkeys and ducks.
Canine influenza virus (CIV) of the H3N8 subtype has emerged in dog populations throughout the United States where it has become endemic in kennels and animal shelters in some regions. It has not previously been determined whether the canine-adapted H3N8 influenza virus can be transmitted to chickens, turkeys or ducks which are economically important animals that are susceptible to type A influenza virus from numerous species. Four-week-old specific pathogen-free (SPF) chickens, 3-week-old SPF turkeys and 2-week-old commercial Pekin ducks were inoculated with 10(5·2) 50% tissue culture infectious doses of CIV per bird by the intra-choanal route. The birds were observed daily, and at 2 and 4 days post-inoculation (DPI), two inoculated birds and one sham-inoculated control bird were euthanized and necropsied to evaluate gross lesions and to collect tissues for microscopic examination. Cloacal and oral swabs were collected at 2, 4 and 7 DPI to evaluate virus shed by real-time RT-PCR (rRT-PCR). Two weeks post-infection, sera were collected from all remaining birds for type A influenza antibody detection by hemagglutination inhibition assay. Clinical signs and gross lesions were not observed in any of the birds of any species nor did any seroconvert. Oral and Cloacal swab material was negative for virus by rRT-PCR. Chickens, turkeys and Pekin ducks are not susceptible to infection with CIV by simulated respiratory exposure route with the dose administered.


Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine transporter.
Concurrent cocaine and alcohol use is common practice in the general population, as indicated by recent prevalence studies. In the presence of ethyl alcohol, cocaine is metabolized to its ethyl homolog, cocaethylene. The transesterification of cocaine and ethanol to cocaethylene takes place in the liver and represents a novel metabolic reaction. Cocaethylene was detected in postmortem blood, liver, and neurological tissues in concentrations equal to and sometimes exceeding those of cocaine. In vitro binding studies demonstrate that cocaethylene has a pharmacological profile similar but not identical to that of cocaine at monoamine transport sites assayed in the human brain. Cocaethylene was equipotent to cocaine at inhibiting [3H]mazindol binding to the dopamine transporter. The blockade of dopamine reuptake in the synaptic cleft by cocaethylene may account for the enhanced euphoria associated with combined alcohol and cocaine abuse.


Roles of DLT in fine modulation on brassinosteroid response in rice.
Accumulated evidences suggest that brassinosteroid (BR) response is fine-tuned by multiple strategies. Recently, a GRAS protein, DLT, was identified to be involved in rice BR signaling. Transcription analysis of most known BR-related genes, including biosynthetic genes, signaling genes and also several downstream BR responsive genes, reveals DLT has extensive effects on BR-related genes expression, indicating its important role in modulating BR response. By promoter and protein sequence analysis, a complicated and subtle network was proposed that DLT may be involved in fine-modulating BR response at both transcriptional and protein levels. This provides new insights into BR signaling pathway and also gives a clear direction for the future work.


The prognostic significance of thymidylate synthase and dihydropyrimidine dehydrogenase in colorectal cancer of 303 patients adjuvantly treated with 5-fluorouracil.
Cytotoxic effect of 5-fluorouracil 5-FU is mediated through inhibition of thymidylate synthase (TS), and 5-FU is catabolised by dihydropyrimidine dehydrogenase (DPD). Efficacy of 5-FU may therefore depend on the TS and DPD activity of colorectal cancer. Archival tumour specimens from 303 consecutive patients were analysed for the expression of TS and DPD using immunohistochemistry. All patients were completely resected for colorectal cancer stages II-III and have subsequently received adjuvant treatment with 5-FU. In a multivariate analysis adjusting for the impact of bowel obstruction and vascular tumour invasion, diffuse TS pattern was significantly associated with increased risk of recurrence (hazard ratio (HR) = 1.9; 95% confidence interval (CI): 1.1-3.2; p = 0.02), but without significant association to death (HR = 1.6; 95% CI: 0.9-2.8; p = 0.08). High TS intensity was not significantly associated with lower risk of recurrence (HR = 0.6; 95% CI: 0.3-1.1; p = 0.07) or death (HR = 0.6; 95% CI: 0.3-1.2; p = 0.2). High DPD intensity was significantly associated with increased risk of recurrence (HR = 1.5; 95% CI: 1.1-2.3; p = 0.03) and death (HR = 1.6; 95% CI: 1.1-2.5; p = 0.02). Patients with a combination of low TS and high DPD intensity were at significantly increased risk of both recurrence (HR = 2.1; 95% CI: 1.0-4.2; p = 0.04) and death (HR = 2.0; 95% CI: 1.0-4.0; p = 0.05). No relationship between tolerability and toxicity of 5-FU and TS and DPD expression was found. It is concluded that characterizing colorectal carcinomas by TS and DPD expression may disclose subsets of patients with significantly greater risk of disease recurrence and early death. This may be utilized in the selection of patients for treatment approaches and for decision on follow-up programs.


Identification of Hub Genes in Different Stages of Colorectal Cancer through an Integrated Bioinformatics Approach.
Colorectal cancer (CRC) is the third most common cancer that contributes to cancer-related morbidity. However, the differential expression of genes in different phases of CRC is largely unknown. Moreover, very little is known about the role of stress-survival pathways in CRC. We sought to discover the hub genes and identify their roles in several key pathways, including oxidative stress and apoptosis in the different stages of CRC. To identify the hub genes that may be involved in the different stages of CRC, gene expression datasets were obtained from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) common among the different datasets for each group were obtained using the robust rank aggregation method. Then, gene enrichment analysis was carried out with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Finally, the protein-protein interaction networks were constructed using the Cytoscape software. We identified 40 hub genes and performed enrichment analysis for each group. We also used the Oncomine database to identify the DEGs related to stress-survival and apoptosis pathways involved in different stages of CRC. In conclusion, the hub genes were found to be enriched in several key pathways, including the cell cycle and p53 signaling pathway. Some of the hub genes were also reported in the stress-survival and apoptosis pathways. The hub DEGs revealed from our study may be used as biomarkers and may explain CRC development and progression mechanisms.


M-State and N-Color (M-N = 1-1, 2-1, and 1-2) Turing Algorithms Demonstrated via DNA Self-Assembly.
The fast and extensive generation of patterns using specific algorithms is a major challenge in the field of DNA algorithmic self-assembly. Turing machines (TMs) are simple computable machines that execute certain algorithms using carefully designed logic gates. We investigate Turing algorithms for the generation of patterns on algorithmic lattices using specific logic gates. Logic gates can be implemented into Turing building blocks. We discuss comprehensive methods for designing Turing building blocks to demonstrate an M-state and N-color Turing machine (M-N TM). The M-state and N-color (M-N = 1-1, 2-1, and 1-2) TMs generate Turing patterns that can be fabricated via DNA algorithmic self-assembly. The M-N TMs require two-input and three-output logic gates. We designed the head, tape, and transition rule tiles to demonstrate TMs for the 1-1, 2-1, and 1-2 Turing algorithms. By analyzing the characteristics of the Turing patterns, we classified them into two classes (DL and DR for states grown diagonally to the left and right, respectively) for the 1-1 TM, three for the 2-1 TM, and nine for the 1-2 TM. Among these, six representative Turing patterns generated using rules R11-0 and R11-1 for 1-1 TM, R21-01 and R21-09 for 2-1 TM, and R12-02 and R12-08 for 1-2 TM were constructed with DNA building blocks. Turing patterns on the DNA lattices were visualized by atomic force microscopy. The Turing patterns on the DNA lattices were similar to those simulated patterns. Implementing the Turing algorithms into DNA building blocks, as demonstrated via DNA algorithmic self-assembly, can be extended to a higher order of state and color to generate more complicated patterns, compute arithmetic operations, and solve mathematical functions.


Activation of spinal dorsal horn P2Y13 receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain.
The dorsal horn P2Y13 receptor is involved in the development of pain behavior induced by peripheral nerve injury. It is unclear whether the expression of proinflammatory cytokines interleukin (IL)-1β and IL-6 at the spinal dorsal horn are influenced after the activation of P2Y13 receptor in rats with diabetic neuropathic pain (DNP). A rat model of type 1 DNP was induced by intraperitoneal injection of streptozotocin (STZ). We examined the expression of P2Y13 receptor, Iba-1, IL-1β, IL-6, JAK2, STAT3, pTyr1336, and pTyr1472 NR2B in rat spinal dorsal horn. Compared with normal rats, STZ-diabetic rats displayed obvious mechanical allodynia and the increased expression of P2Y13 receptor, Iba-1, IL-1β, and IL-6 in the dorsal spinal cord that was continued for 6 weeks in DNP rats. The data obtained indicated that, in DNP rats, administration of MRS2211 significantly attenuated mechanical allodynia. Compared with DNP rats, after MRS2211 treatment, expression of the P2Y13 receptor, Iba-1, IL-1β, and IL-6 were reduced 4 weeks after the STZ injection. However, MRS2211 treatment did not attenuate the expression of the P2Y13 receptor, Iba-1, IL-1β, and IL-6 at 6 weeks after the STZ injection. MRS2211 suppressed JAK2 and STAT3 expression in the early stage, but not in the later stage. Moreover, pTyr1336 NR2B was significantly decreased, whereas pTyr1472 NR2B was unaffected in the dorsal spinal cord of MRS2211-treated DNP rats. Intrathecal MRS2211 produces an anti-nociceptive effect in early-stage DNP. A possible mechanism involved in MRS2211-induced analgesia is that blocking the P2Y13 receptor downregulates levels of IL-1β and IL-6, which subsequently inhibit the activation of the JAK2/STAT3 signaling pathway. Furthermore, blocking the activation of the P2Y13 receptor can decrease NR2B-containing NMDAR phosphorylation in dorsal spinal cord neurons, thereby attenuating central sensitization in STZ-induced DNP rats.


Characterisation of (E)-2-styrylchromones by electrospray ionisation mass spectrometry: singular gas-phase formation of benzoxanthenones.
The electrospray ionisation (ESI) mass spectra (ESI-MS(n) , n = 2 and 3) of six (E)-2-styrylchromones containing electron-donating and electron-withdrawing groups were studied for the first time. The potential application of these compounds as drug candidates brings a need for the development of an analytical method to ensure a detailed knowledge of their structures. ESI-MS, CID-MS(2) and MS(3) spectra of all the studied compounds were acquired using a LXQ linear ion trap mass spectrometer with an electrospray source, operating in the positive ion mode. ESI conditions were: nitrogen 8.00 sheath gas flow rate (arb), spray voltage 5 kV, heated capillary temperature 275 °C, capillary voltage 10.99 V and tube lens voltage 75.01 V. CID-MS(2) and MS(3) experiments were performed on mass-selected precursor ions using standard isolation and excitation procedures (activation q value of 0.25, activation time of 30 ms). A comparable pattern of product ions was observed for all the studied compounds. Only the product ion ((1,2)(3,4)) A(+) is common to all the studied compounds. Common to compounds 1 (R(2) = H), 1a (R(2) = OMe) and 1c (R(2) = Cl) are the product ions formed by loss of H(2)O, CO, C(6)H(5)OH, and the product ions ((1,2)(2,3))B(+) and ((1,2)(3,4))B(+). Among all compounds, 2-SC 1b (R(2) = NO(2)) shows an obvious differentiation showing the lowest number of product ions under CID-MS(2) conditions. The analysed compounds revealed a comparable pattern of product ions formed for each compound only different in what concerns the relative abundance of these formed product ions. A rather interesting and unexpected loss of 2 Da was observed for some compounds. The structure of a benzoxanthenone was proposed for this product ion based on evidence obtained by synthesised benzoxanthenone as a model compound.


Establishing a Split Luciferase Assay for Proteinkinase G (PKG) Interaction Studies.
Nitric oxide (NO/cyclic guanosine monophosphate (cGMP)-regulated cellular mechanisms are involved in a variety of (patho-) physiological processes. One of the main effector molecules in this system, proteinkinase G (PKG), serves as a molecular switch by phosphorylating different target proteins and thereby turning them on or off. To date, only a few interaction partners of PKG have been described although the identification of protein-protein interactions (PPI) is indispensable for the understanding of cellular processes and diseases. Conventionally used methods to detect PPIs exhibit several disadvantages, e.g., co-immunoprecipitations, which depend on suitable high-affinity antibodies. Therefore, we established a cell-based protein-fragment complementation assay (PCA) for the identification of PKG target proteins. Here, a reporter protein (click beetle luciferase) is split into two fragments and fused to two different possible interaction partners. If interaction occurs, the reporter protein is functionally complemented and the catalyzed reaction can then be quantitatively measured. By using this technique, we confirmed the regulator of G-Protein signaling 2 (RGS2) as an interaction partner of PKGIα (a PKG-isoform) following stimulation with 8-Br-cGMP and 8-pCPT-cGMP. Hence, our results support the conclusion that the established approach could serve as a novel tool for the rapid, easy and cost-efficient detection of novel PKG target proteins.


Vibrational structure of titanium silicate catalysts. A spectroscopic and theoretical study.
A thorough analysis of the vibrational features of the titanium silicalite-1 (TS-1) catalyst is presented, based on quantitative IR measurements, Raman and resonant Raman experiments, quantitative XANES, and quantum chemical calculations on cluster and periodic models. The linear correlation of the intensity of the IR and Raman bands located at 960 and 1125 cm(-1) and the XANES peak at 4967 eV with the amount of tetrahedral Ti are quantitatively demonstrated. Raman and resonant Raman spectra of silicalite and TS-1 with variable Ti content are presented, showing main features at 960 and 1125 cm(-1) associated with titanium insertion into the zeolite framework. The enhancement of the intensity of the 1125 cm(-1) feature and the invariance of the 960 cm(-1) feature in UV-Raman experiments, are discussed in terms of resonant Raman selection rules. Quantum chemical calculations on cluster models Si[OSi(OH)(3)](4) and Ti[OSi(OH)(3)](4) at the B3LYP/6-31G(d) level of theory provide the basis for the assignment of the main vibrational contributions and for the understanding of Raman enhancement. The resonance-enhanced 1125 cm(-1) mode is unambiguously associated with a totally symmetric vibration of the TiO(4) tetrahedron, achieved through in-phase antisymmetric stretching of the four connected Ti-O-Si bridges. This vibration can also be described as a totally symmetric stretching of the four Si-O bonds pointing toward Ti. The resonance enhancement of this feature is explained in terms of the electronic structure of the Ti-containing moiety. Asymmetric stretching modes of TO(4) units show distinct behavior when (i) T is occupied by Si as in perfect silicalite, (ii) T is occupied by Ti as in TS-1, or (iii) the oxygen atom belongs to an OH group, such as in terminal tetrahedra of cluster models and in real defective zeolites. Asymmetric SiO(4) and TiO(4) stretching modes appear above and below 1000 cm(-1), respectively, when they are achieved through antisymmetric stretching of the T-O-Si bridges, and around 800 cm(-1) (in both SiO(4) and TiO(4)) when they involve symmetric stretching of the T-O-Si units. In purely siliceous models, the transparency gap between the main peaks at 800 and 1100 cm(-1) contains only vibrational features associated with terminal Si-OH groups, while in Ti-containing models it contains also the above-mentioned asymmetric TiO(4) modes, which in turn are strongly coupled with Si-OH stretching modes. Calculations on periodic models of silicalite and TS-1 free of OH groups using the QMPOT embedding method correctly reproduce the transparency gap of silicalite and the appearance of asymmetric TiO(4) vibrations at 960 cm(-1) in TS-1. Finally, we demonstrate, for the first time, that the distortion of the tetrahedral symmetry around Ti caused by water adsorption quenches the UV-Raman enhancement of the 1125 cm(-1) band.


Management of antithrombotic therapy in patients undergoing electrophysiological device surgery.
The aim of this review is to formulate practical recommendations for the management of antithrombotic therapy in patients undergoing cardiac implantable electronic device (CIED) surgery by providing indications for a systematic approach to the problem integrating general technical considerations with patient-specific elements based on a careful evaluation of the balance between haemorrhagic and thromboembolic risk. Hundreds of thousands patients undergo implantation or replacement of CIEDs annually in Europe, and up to 50% of these subjects receive antiplatelet agents or oral anticoagulants. The rate of CIED-related complications, mainly infective, has also significantly increased so that transvenous lead extraction procedures are, consequently, often required. Cardiac implantable electronic device surgery is peculiar and portends specific intrinsic risks of developing potentially fatal haemorrhagic complications; on the other hand, the periprocedural suspension of antithrombotic therapy in patients with high thromboembolic risk cardiac conditions may have catastrophic consequences. Accordingly, the management of the candidate to CIED surgery receiving concomitant antithrombotic therapy is a topic of great clinical relevance yet controversial and only partially, if at all, adequately addressed in evidence-based current guidelines. In spite of the fact that in many procedures it seems reasonably safe to proceed with aspirin only or without interruption of anticoagulants, restricting to selected cases the use of bridging therapy with parenteral heparins, there are lots of variables that may make the therapeutic choices challenging. The decision-making process applied in this document relies on the development of a stratification of the procedural haemorrhagic risk and of the risk deriving from the suspension of antiplatelet or anticoagulant therapy combined to generate different clinical scenarios with specific indications for optimal management of periprocedural antithrombotic therapy.


The nuclear lamina binds the EBV genome during latency and regulates viral gene expression.
The Epstein Barr virus (EBV) infects almost 95% of the population worldwide. While typically asymptomatic, EBV latent infection is associated with several malignancies of epithelial and lymphoid origin in immunocompromised individuals. In latently infected cells, the EBV genome persists as a chromatinized episome that expresses a limited set of viral genes in different patterns, referred to as latency types, which coincide with varying stages of infection and various malignancies. We have previously demonstrated that latency types correlate with differences in the composition and structure of the EBV episome. Several cellular factors, including the nuclear lamina, regulate chromatin composition and architecture. While the interaction of the viral genome with the nuclear lamina has been studied in the context of EBV lytic reactivation, the role of the nuclear lamina in controlling EBV latency has not been investigated. Here, we report that the nuclear lamina is an essential epigenetic regulator of the EBV episome. We observed that in B cells, EBV infection affects the composition of the nuclear lamina by inducing the expression of lamin A/C, but only in EBV+ cells expressing the Type III latency program. Using ChIP-Seq, we determined that lamin B1 and lamin A/C bind the EBV genome, and their binding correlates with deposition of the histone repressive mark H3K9me2. By RNA-Seq, we observed that knock-out of lamin A/C in B cells alters EBV gene expression. Our data indicate that the interaction between lamins and the EBV episome contributes to the epigenetic control of viral gene expression during latency, suggesting a restrictive function of the nuclear lamina as part of the host response against viral DNA entry into the nucleus.


Metabolic control and cardiovascular risk factors in type 2 diabetes mellitus patients according to diabetes duration.
Control of glycaemic levels as well as cardiovascular risk factors (CVRF) is essential to prevent the onset of complications associated with type 2 diabetes mellitus (T2DM). To describe the degree of glycaemic control and CVRF in relation to diabetes duration. Multicentre cross-sectional study in T2DM patients seen in primary care centres during 2007. Demographical and clinical characteristics, antidiabetic treatments and development of disease complications. Diabetes duration classification: 0-5, 6-10, 11-20 and >20 years. Logistic regression models were used in the analysis. A total of 3130 patients; 51.5% males; mean age: 68±11.7 years; mean diabetes duration:7.0 (±5.6) years, median: 5 (interquartile range:3-9) years; mean HbA1c: 6.84 (±1.5), were analyzed. There has been a progressive decline in HbA1c levels (HbA1c > 7% in 25.8% of patients during the first 5 years and 51.8% after 20 years). Blood pressure values remained relatively stable throughout disease duration. The mean value of low density lipoprotein (LDL) experienced a slight decline with the progression of the disease, but due to the significant increase of cardiovascular disease (CVD) after 20 years of duration, less patients reached the recommended target (LDL < 100mg/dl) in secondary prevention. Logistic regression model controlling for age, sex and CVD showed that diabetes duration was related to glycaemic control (odds ratio: 1.066, 95% confidence interval: 1.050-1.082 per year) but not to blood pressure or LDL control. The degree of glycaemic control and the risk factors in relation to the duration of T2DM followed different patterns. Diabetes duration was associated with a poorer glycaemic control but in general had a limited role in blood pressure control or lipid profile.


Structural Chemistry of Human SET Domain Protein Methyltransferases.
There are about fifty SET domain protein methyltransferases (PMTs) in the human genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to substrate lysines on histone tails or other peptides. A number of structures in complex with cofactor, substrate, or inhibitors revealed the mechanisms of substrate recognition, methylation state specificity, and chemical inhibition. Based on these structures, we review the structural chemistry of SET domain PMTs, and propose general concepts towards the development of selective inhibitors.


Medieval Gilding Technology of Historical Metal Threads Revealed by Electron Optical and Micro-Raman Spectroscopic Study of Focused Ion Beam-Milled Cross Sections.
Although gilt silver threads were widely used for decorating historical textiles, their manufacturing techniques have been elusive for centuries. Contemporary written sources give only limited, sometimes ambiguous information, and detailed cross-sectional study of the microscale soft noble metal objects has been hindered by sample preparation. In this work, to give a thorough characterization of historical gilt silver threads, nano- and microscale textural, chemical, and structural data on cross sections, prepared by focused ion beam milling, were collected, using various electron-optical methods (high-resolution scanning electron microscopy (SEM), wavelength-dispersive electron probe microanalysis (EPMA), electron backscattered diffraction (EBSD) combined with energy-dispersive electron probe microanalysis (EDX), transmission electron microscopy (TEM) combined with EDX, and micro-Raman spectroscopy. The thickness of the gold coating varied between 70-400 nm. Data reveal nano- and microscale metallurgy-related, gilding-related and corrosion-related inhomogeneities in the silver base. These inhomogeneities account for the limitations of surface analysis when tracking gilding methods of historical metal threads, and explain why chemical information has to be connected to 3D texture on submicrometre scale. The geometry and chemical composition (lack of mercury, copper) of the gold/silver interface prove that the ancient gilding technology was diffusion bonding. The observed differences in the copper content of the silver base of the different thread types suggest intentional technological choice. Among the examined textiles of different ages (13th-17th centuries) and provenances narrow technological variation has been found.


Inhibition of Propionibacterium acnes-induced mediators of inflammation by Indian herbs.
Propionibacterium acnes, an anaerobic pathogen, plays an important role in the pathogenesis of acne by inducing certain inflammatory mediators. These mediators include reactive oxygen species (ROS) and pro-inflammatory cytokines. In the present study, ROS, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were used as the major criteria for the evaluation of anti-inflammatory activity. To prove the anti-inflammatory effects of herbs, polymorphonuclear leukocytes (PMNL) and monocytes were treated with culture supernatant of P. acnes in the presence or absence of herbs. It was found that Rubia cordifolia, Curcuma longa, Hemidesmus indicus, and Azadirachta indica caused a statistically significant suppression of ROS from PMNL. Sphaeranthus indicus caused a smaller, still significant suppression of ROS. Aloe vera had no effect on ROS production. In the case of proinflammatory cytokine-induced monocytes, maximum suppression was shown by Azadirachta indica and Sphaeranthus indicus, followed by Hemidesmus indicus, Rubia cordifolia, and Curcuma longa. Aloe vera showed insignificant inhibitory activity. Thus, these herbs shows anti-inflammatory activity by suppressing the capacity of P. acnes-induced ROS and pro-inflammatory cytokines, the two important inflammatory mediators in acne pathogenesis.


Antecedent medical diseases in patients with amyotrophic lateral sclerosis. A population-based case-controlled study in Rochester, Minn, 1925 through 1987.
Odds ratios (ORs) were estimated for the prevalence of antecedent endocrine, metabolic, or vascular diseases among 45 patients with amyotrophic lateral sclerosis from the Rochester, Minn, population compared with 90 control subjects matched for sex, year of birth, period of observation, and residence. Hypertension occurred less frequently in male patients with amyotrophic lateral sclerosis (4%) than in control subjects (30%; OR = .10). Because of small population size, no conclusions can be drawn with respect to the following antecedent conditions: thyroid disease (OR = 1.61), coronary artery disease (OR = .58), obesity (OR = .52), diabetes (OR = 1.00), cerebrovascular disease (OR = .21), and peripheral vascular disease (OR = 1.23). The heterogeneity of antecedent thyroid disease makes it highly unlikely that any specific thyroid lesion is causally associated with most cases of amyotrophic lateral sclerosis. Hypertension may be a marker for protective factors against the development of amyotrophic lateral sclerosis in men.


The importance of developing relevant animal models to assess existing and new materials.
We summarize the recent literature on the use of different animal models for testing existing and new materials for treatment of pelvic organ prolapse. A wide spectrum of animal models is being used in urogynecology, both for the study of physiologic and pathophysiologic processes, training in surgical procedures, yet mainly to study the host response to implant materials. The quality of studies is variable, and procedures, read-outs, and reporting are not standardized. This makes comparison very difficult. The research community is experimenting with different knitting patterns, novel polymers, bioactivation, as well as resorbable rather than durable implants. Outcomes of the experiments are dependent on the location of implantation. Lighter polypropylene constructs seem to induce a less vigorous host response than elder heavier products. Modification of the surface yields contradictory findings. Resorbable acellular collagen matrices may be reintroduced as prophylactically inserted support structures. Although animal experimentation with novel candidate implants is advocated, there is a lack of standardization in reporting. The concept of resorbable construct is being revived, as durable materials have caused clinical graft-related complications. Large animal experiments seem to provide interesting and more comprehensive information, yet their use may be contested.


Breast self-examination in relation to the occurrence of advanced breast cancer.
Two hundred nine female enrollees of the Group Health Cooperative of Puget Sound who developed advanced-stage breast cancer during the period 1982-1988 were interviewed about their practice of breast self-examination (BSE), use of other breast cancer screening modalities, and medical and reproductive histories. Each subject's description of how she performed the examination was scored according to her mention of up to 10 recommended BSE techniques. A random sample of 433 women without advanced-stage breast cancer from the same population was interviewed for comparison. Relative to women not practicing BSE, the risk of advanced-stage breast cancer among BSE users was 1.15 (95% confidence interval, 0.73-1.81). Frequency of BSE did not differ between women with advanced-stage breast cancer and control subjects, whether in all subjects or in subgroups defined by age, use of mammography, or frequency of clinical breast examinations. While self-described proficiency in BSE was generally low in both case and control subjects, the small percentage of women reporting more thorough self-examinations, regardless of frequency, had about a 35% decrease in the occurrence of advanced-stage breast cancer compared to women who did not perform BSE. These results suggest that, while carefully performed BSE may avoid the development of some advanced-stage breast cancers, BSE as practiced by most Seattle-area women is of little or no benefit.


Biomechanical comparison of acromioclavicular joint reconstructions using coracoclavicular tendon grafts with and without coracoacromial ligament transfer.
The purpose of this study was to compare the initial strength of acromioclavicular joint reconstructions using coracoclavicular (CC) tendon grafts with and without coracoacromial (CA) ligament transfers. Two different acromioclavicular joint reconstructions were performed in 7 matched pairs of cadaveric shoulders. Paired shoulders were repaired with either a hamstring allograft CC reconstruction (group 1) or a hamstring allograft CC reconstruction plus a CA ligament transfer (group 2). Intact specimens and then reconstructions were cycled from 0 to 100 N at 1 Hz for 100 cycles in a superior direction, and displacements were recorded. Finally, the stiffness of the reconstructions and the ultimate load to failure were recorded. Superior displacement of the reconstructions after cyclic loading was 4.43 ± 1.82 mm in group 1 and 3.75 ± 1.56 mm in group 2 (P = .38). Ultimate load after load to failure was 970.3 ± 361.03 N in group 1 and 952.7 ± 296.89 N in group 2 (P = .94). Finally, stiffness of the reconstructions was 50.6 ± 6.14 N/mm in group 1 and 65.6 ± 18.45 N/mm in group 2 (P = .12). The addition of a transfer of the CA ligament to an acromioclavicular joint reconstruction with a CC hamstring graft does not appear to significantly improve its overall initial biomechanical strength. These data suggest that a CA ligament transfer may add very little to a CC tendon graft reconstruction augmented with high-strength suture with regard to initial, time zero displacement and strength.


Knowledge, attitude and practices toward pharmacovigilance and adverse drug reactions in postgraduate students of Tertiary Care Hospital in Gujarat.
Being key health care professional, physicians, pharmacist and nurses have immense responsibility in reporting adverse drug reaction (ADR). Therefore, the study objective was to evaluate the knowledge, attitude and practices (KAP) toward pharmacovigilance and ADRs of postgraduate students of our institute. A cross-sectional questionnaires based study was carried out in postgraduate students of the clinical department at tertiary care hospital attached with Govt. Medical College, Vadodara, Gujarat (India). A total of 22 questionnaires about KAP toward ADRs and pharmacovigilance were developed and peer viewed of all questionnaires by expert faculties from our institute. We were contacted directly to postgraduate students of respective clinical department; questionnaires were distributed and taken back after 30 min. The filled KAP questionnaires were analyzed in question wise and their percentage value was calculated by using Microsoft Excel spreadsheet. Postgraduate residents (n = 101) from different clinical departments were enrolled in the study. Average 34.83% correct and 64.08% incorrect knowledge about ADRs and pharmacovigilance and an average 90.76% students were agreed to reporting ADRs is necessary, mandatory and increased patient's safety. Only 7.92% of postgraduate doctors were reported ADR at institute or ADR reporting center. We concluded that postgraduate students have a better attitude toward reporting ADRs, but have lack of knowledge and poor practices of ADRs. The majority of postgraduate students were felt ADR reporting and monitoring is very important, but few had ever reported ADRs because of lack of sensitization and knowledge of pharmacovigilance and ADR.


Application of helical tomotherapy for two cases of advanced hepatocellular carcinoma.
The role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) has been limited to date, because the liver has a low tolerance to radiation. However, reconstructing tumors and surrounding organs via a three-dimensional conformal planning system can avoid excess radiotherapy exposure to the rest of the liver and adjacent organs. Recently, the concept of "adaptive radiotherapy," such as with helical tomotherapy, has been introduced for treating HCC. Helical tomotherapy obtains an image from the computed tomography component, which allows targeted regions to be visualized prior to, during, and immediately after each treatment and delivers intensity-modulated radiation therapy. We report two patients with advanced HCC who underwent tomotherapy treatment. One was a patient afflicted with advanced HCC and a portal vein tumor thrombus, which was treated with tomotherapy combined with transarterial chemolipiodolization. The other was a patient afflicted with multiple pulmonary metastases treated with tomotherapy followed by systemic chemotherapy.


Oromandibular limb hypogenesis and gastroschisis.
The oromandibular limb hypogenesis syndromes (OLHS), which are congenital malformations involving the tongue, mandible, and the limbs are extremely rare with a few sporadic cases reported in the literature. In this report, the authors report a case of OLHS with gastroschisis, that has not been described previously according to the medline search.


[Computerized processing of two-dimensional echo-cardiograms: its application for quantitating left ventricular regional contractility and three-dimensional echocardiography].
This study assessed the computerized processing of two-dimensional echocardiograms for quantitating left ventricular regional contractility and for computer reconstruction of the left ventricle; so-called three-dimensional echocardiography. Computer analysis of two-dimensional echocardiograms for quantitative evaluations of the left ventricular regional contractility in myocardial infarction: A new practical method for computer digital image processing of two-dimensional echocardiograms was developed for quantitating left ventricular regional contractility. Short-axis cross-sectional images of the left ventricle at the levels of the mitral valve (MV), papillary muscles (PM) and the apex (AP) were recorded using a phased array sector scanner in thirty patients with healed myocardial infarction and fifteen normal control subjects. The echocardiographic data were recorded on the video tape and transferred to a minicomputer via interface circuits, digitized, and processed automatically. Each digitized image consisted of 256 X 256 pixels with a gray scale of 256 values. The edges of the endocardial and epicardial walls were detected by applying sequential steps including smoothing, dynamic thresholding, region growing, and filling of small holes. The rationale of edge detection depended on assuming that abrupt changes in gray levels occurred at the boundary, and that the points with maximum gradient values were boundaries of the left ventricular wall. Best-fit contours of endocardial and epicardial edges were drawn by fitting a spline. Besides this automatic edge tracing, endocardial and epicardial edges were also manually traced using a digi-pen system, whose results coincided well with automatic tracings. After detection of edges of endocardial and epicardial walls, the short-axis cross sectional left ventricular wall at each level was divided into eight segments. The geometric center of the end-diastolic left ventricular cavity and the axis connecting this with the posterior end of the right side of the septum was used as the reference point and line (fixed reference system). End-diastolic and end-systolic segmental hemiaxes, segmental area, segmental wall thickness and changes during the cardiac cycle were measured and calculated automatically in each segment using a computer. Regional contractility of the left ventricle was evaluated by percent systolic changes of the segmental hemiaxis, area and wall thickness. These values were significantly reduced in the infarcted left ventricular wall as defined by left ventriculography and coronary angiography.(ABSTRACT TRUNCATED AT 400 WORDS)


[Genetic analysis of Friedreich's ataxia using polymorphic DNA markers].
Friedreich's ataxia (FA) is a progressive degenerative disease involving both central and peripheral nervous system. It is an autosomal recessive hereditary disorder, which begins around puberty and has an unknown genetic basis and biochemical defect. The recent mapping of FA locus in human chromosome 9 by means of the analysis of the molecular genetic linkage has permitted to evaluate FA genetics with polymorphic genetic markers (RFLPs) that are secreted linked with the FA gene. The normal and mutant allele secretion of FA was evaluated in ten Spanish families with one or two members with FA by means of several cloned probes (MCT112, DR47, D9S1 and HHH220), localized in chromosome 9 and strongly linked to FA gene, with the aim of achieving a predictive diagnosis of relatives in the pediatric age and to detect healthy carriers. In 9 out of 10 families some totally or partially informative RFLP were found. In 5 of 6 relatives in pediatric age the future development of the disease could be ruled out. By contrast, the carrier status could only be identified in three relatives. In a family with two affected children a genetic recombinant for D9S1 was found. Remarkably, one of them had a better clinical evolution and preserved tendon reflexes in lower limbs.


The Effect of Nutrition Education Using MyPlate on Lipid Profiles, Glycemic Indices, and Inflammatory Markers in Diabetic Patients.
As a result of a nutrition transition, chronic diseases, including diabetes, have increased in Iran. Nutrition education is a cost-effective method for modifying diet and controlling diabetes. This study aimed to examine the effect of nutrition education using MyPlate recommendations on glycemic and lipid profiles and inflammatory markers in Iranian adults diagnosed with type 2 diabetes. A 12-week randomized clinical trial was conducted on 44 adults aged 30-50 years from Ahvaz, Iran. The participants were divided into education and control groups. The education participants were taught the MyPlate recommendations. Serum levels of fasting blood sugar (FBS), hemoglobin A1c (HbA1c), lipid profiles, and inflammatory markers, including high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α, and adiponectin, were measured at the baseline and the end of the study. The results showed that serum levels of FBS (p = 0.014) and HbA1c (p < 0.001) decreased significantly in the education group at the end of the study. The serum level of low-density lipoprotein in the education group declined significantly at the end of the study (p = 0.043). Furthermore, the serum level of hs-CRP (p = 0.005) declined significantly while the level of adiponectin (p = 0.035) increased in the education group at the end of the study. The evidence of this study showed that nutrition education using MyPlate recommendations is an effective method for controlling diabetes complications. A longitudinal analysis with a larger sample size is recommended to confirm the evidence of this study. Iranian Registry of Clinical Trials Identifier: IRCT2015031921443N2.


[Diagnosis of myocardial ischemia using functional ST mapping and 201Tl stress scintigraphy].
The authors compared the value of two non-invasive methods in the diagnosis of myocardial ischaemia, i.e. precordial working maps of the ST segment and working scintigraphy of the myocardium with 201T1 after a load. On comparison with the finding on the coronary arteries, the authors found a high sensitivity of mapping, 89.3%, and of 201T1 scan, 92.9%, while the specificity of both methods was lower, 57.1%. Both methods are equally valuable for diagnosis of myocardial ischaemia; for assessment of the site of affection thallium scintigraphy of the myocardium is preferable.


Quantum signatures of chaos, thermalization, and tunneling in the exactly solvable few-body kicked top.
Exactly solvable models that exhibit quantum signatures of classical chaos are both rare as well as important-more so in view of the fact that the mechanisms for ergodic behavior and thermalization in isolated quantum systems and its connections to nonintegrability are under active investigation. In this work, we study quantum systems of few qubits collectively modeled as a kicked top, a textbook example of quantum chaos. In particular, we show that the three- and four-qubit cases are exactly solvable and yet, interestingly, can display signatures of ergodicity and thermalization. Deriving analytical expressions for entanglement entropy and concurrence, we see agreement in certain parameter regimes between long-time average values and ensemble averages of random states with permutation symmetry. Comparing with results using the data of a recent transmons-based experiment realizing the three-qubit case, we find agreement for short times, including a peculiar steplike behavior in correlations of some states. In the case of four qubits we point to a precursor of dynamical tunneling between what in the classical limit would be two stable islands. Numerical results for larger number of qubits show the emergence of the classical limit including signatures of a bifurcation.


Two new antimicrobial lysoplasmanylinositols from the marine sponge Theonella swinhoei.
Two new antimicrobial lysoplasmanylinositols have been isolated from the marine sponge Theonella swinhoei. Their structures were elucidated on the basis of spectroscopic and chemical analysis.


Well-being in Dinka refugee women of southern Sudan.
The purpose of this study was to understand the health and well-being of Sudanese refugee women who were resettled with their children to the United States. The design was an interpretive ethnography using individual interviews and participant observation with extensive field notes. The findings describe personal factors as well as community and social conditions that influenced the health and well-being of the refugee women and their families. These influences are captured in the three themes that emerged from the study: (1) liminality--living between two cultures, (2) self-support--standing on our own two legs, and (3) hope for the future. These themes describe a process of how refugee women achieve well-being in the transition to a new country and culture. The study contributes to our theoretical understanding of how to develop culturally congruent interventions for resettled refugees.


Concepts of depression: sporadic revolutions of continuous evolution.
The classification of depressive disorders has been changing ever since the first descriptions of mood disorders were produced some 2500 years ago. The interest in their classification has recently been revived as a result of the introduction of new types of medicaments for the treatment of the disorders belonging to the spectrum of mood disorders and of the emphasis that has been given to the diagnosis and treatment of mental disorders, and in particular depression in primary health care services. The currently used systems of classification contain a relatively large number of categories reserved for depressive disorders and it is to be hoped that the experience and information obtained by the use of these classifications, as well as the results of research into the psychopathology and the effects of treatment of mood disorders, will make it possible to arrive at a simplified and better classification of these conditions. It is likely that this improvement will be incremental, that the development of significantly better classifications will take time and the result of this developmental process will be a classification that will reflect consensus of the mental health professions based on the best available evidence. Copyright 2001 John Wiley & Sons, Ltd.


A series of supernumerary small ring marker autosomes identified by FISH with chromosome probe arrays and literature review excluding chromosome 15.
Seven supernumerary small ring marker autosomes were studied. The pantelomere probe (Oncor) in conjunction with scoring for dicentric rings was used to confirm ring morphology. The small rings were identified mainly by FISH with chromosome probe arrays (Cytocell) containing representations from all 24 chromosomes and the rings were derived from chromosomes 7, 8 (three cases), 11, 12, and 14. The effectiveness of the array methodology in identifying markers was tested. Microsatellite DNA data showed biparental disomy (BPD) was present for the rings from chromosomes 7 and 14 thereby excluding UPD, both were de novo but the ring 14 was of paternal origin. The literature on supernumerary small ring autosomes was reviewed excluding chromosome 15. The grade and distribution of mosaicism was invoked as the major determinant of the differences in phenotype and, in addition, variation was attributed to the possibility of different contributions from each chromosome arm. There are 88 published supernumerary small ring cases in total, with phenotypic data attributable to the respective rings in 77 cases and all chromosomes being represented except chromosome 17. Of the prenatally ascertained cases, where there was adequate phenotypic data, 30% had an abnormal phenotype attributable to the ring, and there were 44% familial cases in this group. Of the postnatally ascertained small rings, 75% had an abnormal phenotype attributable to the ring and there were 13% familial cases. This higher abnormality rate is concordant with the considerable ascertainment bias of this latter group and the prenatal data are recommended for genetic counseling. Although data are small there were some differences between the rings derived from different chromosomes. Chromosomes 3 and 8 demonstrate the extremes. Of the supernumerary small r(8) cases reviewed including the three presently described, 8/11 had an abnormal phenotype attributable to the marker but of the small r(3) cases, only 1/6 had an abnormal phenotype. Two of the present r(8) were studied with the GATA4 probe at 8p23.1. The r(8) in case 2 (patient moderately retarded) was comprised mostly of an intact 8p whereas the larger r(8) in case 3 (normal phenotype) was missing 8p23.1 --> pter and had more of 8q contributing to the ring. In other supernumerary rings postnatally ascertained, there is mostly insufficient data but there is an abnormal phenotype in 8/11 cases with multiple small rings, in 5/6 cases with r(20), and in 5/10 with r(1). A novel origin for supernumerary small rings is proposed: that they may originate from incompletely digested superfluous (haploid) pronuclei. The small rings presumptively so formed may occasionally be transfected into the zygote nucleus. The high proportion ( approximately 12.5%) of cases with multiple supernumerary small rings almost always of different centromeric origin is consistent with this concept.


Rapid and facile detection of four date rape drugs in different beverages utilizing proton transfer reaction mass spectrometry (PTR-MS).
In this work, we illustrate the application of proton transfer reaction mass spectrometry (PTR-MS) in the field of food and drink safety. We present proof-of-principle measurements of four different drinks (water, tea, red wine and white wine) each spiked separately with four different date rape drugs (chloral hydrate, tricholorethanol, γ-butyrolactone and butanediol). At first, the ideal PTR-MS operating conditions (reduced electric field strength and monitoring the most abundant [fragment] ion) for detection of the drugs were determined utilizing a time-of-flight-based PTR-MS instrument. We then dissolved small quantities of the drugs (below the activation threshold for effects on humans) into the various types of drinks and detected them using a quadrupole-based PTR-MS instrument via two different sampling methods: (1) dynamic headspace sampling and (2) direct liquid injection. Both methods have their advantages and drawbacks. Only with dynamic headspace sampling can rape drug contaminations be detected within a timeframe of seconds, and therefore, this method is the most promising use of PTR-MS as a fast, sensitive and selective monitor for the detection of food and drink contamination.


Supraclavicular radiotherapy must be limited laterally by the coracoid to avoid significant adjuvant breast nodal radiotherapy lymphoedema risk.
This cross-sectional study aimed to investigate the effect of supraclavicular fossa (SCF) radiotherapy volumes as well as patient characteristics and nodal pathology on the development of lymphoedema. Ninety-one women who had received SCF nodal radiotherapy after axillary dissection were evaluated. Lymphoedema was defined by two measurements: limb volume difference 200 mL, or circumference difference 10 cm proximal or distal to the olecranon>2 cm. On univariate analysis, the addition of axillary to SCF radiotherapy, increasing width of the SCF field, increasing age, presence of extracapsular extension of nodal involvement and use of hormone treatment was associated with lymphoedema by either one or both definitions. For both definitions of lymphoedema, on multivariate analysis, increasing nodal radiotherapy volume remained significant (P=0.02 to 0.007), as did increased age (P=0.05 to 0.001). We conclude that conventionally fractionated SCF radiotherapy limited laterally by the coracoid process has a lymphoedema risk similar to that expected from axillary dissection alone and a lower risk than wider SCF fields with or without an axillary boost.


Effects of NADH-preferring xylose reductase expression on ethanol production from xylose in xylose-metabolizing recombinant Saccharomyces cerevisiae.
Efficient conversion of xylose to ethanol is an essential factor for commercialization of lignocellulosic ethanol. To minimize production of xylitol, a major by-product in xylose metabolism and concomitantly improve ethanol production, Saccharomyces cerevisiae D452-2 was engineered to overexpress NADH-preferable xylose reductase mutant (XR(MUT)) and NAD⁺-dependent xylitol dehydrogenase (XDH) from Pichia stipitis and endogenous xylulokinase (XK). In vitro enzyme assay confirmed the functional expression of XR(MUT), XDH and XK in recombinant S. cerevisiae strains. The change of wild type XR to XR(MUT) along with XK overexpression led to reduction of xylitol accumulation in microaerobic culture. More modulation of the xylose metabolism including overexpression of XR(MUT) and transaldolase, and disruption of the chromosomal ALD6 gene encoding aldehyde dehydrogenase (SX6(MUT)) improved the performance of ethanol production from xylose remarkably. Finally, oxygen-limited fermentation of S. cerevisiae SX6(MUT) resulted in 0.64 g l⁻¹ h⁻¹ xylose consumption rate, 0.25 g l⁻¹ h⁻¹ ethanol productivity and 39% ethanol yield based on the xylose consumed, which were 1.8, 4.2 and 2.2 times higher than the corresponding values of recombinant S. cerevisiae expressing XR(MUT), XDH and XK only.


Thermal performance assessment of heat resistant fabrics based on a new thermal wave model of skin heat transfer.
A thermal wave skin model incorporating surface heat flux from a skin simulant sensor is developed to characterize the thermal performance of heat resistant fabrics covering the skin simulant sensor. Comparisons of time to 2nd-degree skin burn and temperature elevation of skin beneath a layer of fabric between the Pennes' equation and the newly developed thermal wave skin model are performed in this research. Results of tolerance time from the Stoll criterion method are also compared with those from 2 skin models in a thermal protective performance calorimeter. It is concluded that the thermal properties of heat resistant fabrics can be characterized more precisely than previously.


Comparative cardiovascular safety of traditional nonsteroidal anti-inflammatory drugs.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory and analgesic effects. Unfortunately, these drugs are not without toxicity, namely on the gastric mucosa, but also on the cardiovascular system. In this context, the marketing of the coxibs, a new series of NSAIDs that selectively inhibit COX-2, resulted in a large debate around their cardiovascular safety, because they may increase the incidence of myocardial infarction and stroke. The recent suspension of a large, randomised, controlled trial comparing celecoxib, naproxen and placebo in Alzheimer patients (the ADAPT trial) because of an apparent elevated cardiovascular risk in the naproxen group revived the debate on the cardiovascular safety of these drugs, but this time with special emphasis on the effect of traditional nonselective NSAIDs (tNSAIDs). In this paper that reviews and discusses the cardiovascular safety profile of tNSAIDs, essentially naproxen and ibuprofen in view of the most recent experimental and clinical data, the authors note that the published data are quite discordant and one cannot conclude that there is clear evidence to support a cardiovascular hazard from the administration of naproxen or non-naproxen NSAIDs unless additional information is provided. In addition, the results of retrospective case-control studies have to be interpreted very carefully because of the risk of confounding factors that are not always taken into account when subjects were classified either as cases or controls. Thus, in the absence of clear cut data, physicians will have to use traditional NSAIDs (or coxibs) in patients with a high cardiovascular risk on the basis of their common sense rather than on evidence-based medicine. For these patients, one should not forget that an inadequate long-term control of cardiovascular risk factors such as a hypertension, dyslipidaemia, diabetes, smoking and weight excess is more deleterious in terms of cardiovascular mortality than the administration of NSAIDs itself.


Small nanoparticles, surface geometry and contact forces.
In this molecular dynamics study, we examine the local surface geometric effects of the normal impact force between two approximately spherical nanoparticles that collide in a vacuum. Three types of surface geometries-(i) crystal facets, (ii) sharp edges, and (iii) amorphous surfaces of small nanoparticles with radii R<10 nm-are considered. The impact forces are compared with their macroscopic counterparts described by nonlinear contact forces based on Hertz contact mechanics. In our simulations, edge and amorphous surface contacts with weak surface energy reveal that the average impact forces are in excellent agreement with the Hertz contact force. On the other hand, facet collisions show a linearly increasing force with increasing compression. Our results suggest that the nearly spherical nanoparticles are likely to enable some nonlinear dynamic phenomena, such as breathers and solitary waves observed in granular materials, both originating from the nonlinear contact force.


Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by α7 and β2* nicotinic stimulation.
A good model of neuronal death that reproduces the characteristic tau (τ) hyperphosphorylation of Alzheimeŕs disease is the use of okadaic acid (OA). The aim of this study was to determine the contribution of α7 and β2* nicotinic acetylcholine receptor (nAChR) subtypes to neuroprotection against OA in the SH-SY5Y cell line by using the selective α7 and β2* nAChR agonists PNU 282987 and 5-Iodo-A85380, respectively. The results of this study show that both α7 and β2* nAChR can afford neuroprotection against OA-induced neurotoxicity. Protection mediated by α7 nAChRs was independent of Ca(2+) and involved the intracellular signaling pathway Janus Kinase-2/Phosphatidylinositol-3-kinase/Akt. When Ca(2+) entry was promoted through the α7 nAChR by using the α7-selective positive allosteric modulator PNU 120596, protection was lost. By contrast, protection mediated by β2* nAChRs was Ca(2+) dependent and implicated the signaling pathways PI3K/Akt and extracellular regulated kinase 1/2. Both α7 and β2* nAChR activation converged on downregulation of GSK-3β and reduction of τ phosphorylation in cells undergoing cell death induced by OA. Therefore, targeting nAChR could offer a strategy for reducing neurodegeneration secondary to hyperphosphorylation of protein τ.


The relationship between trait mindfulness and subjective wellbeing of kindergarten teachers: The sequential mediating role of emotional intelligence and self-efficacy.
This study explored the relationship between emotional intelligence and self-efficacy in trait mindfulness and subjective wellbeing. In this study, 323 Chinese kindergarten teachers were measured using the Five Facet Mindfulness Questionnaire, Emotional Intelligence Scale, General Self-efficacy Scale, and Subjective Wellbeing Scale. The study found that subjective wellbeing can be predicted directly from trait mindfulness (β = 0.257, p < 0.001). Emotional intelligence could mediate the relationship between trait mindfulness and subjective wellbeing (β = 0.165, p = 0.006). Self-efficacy could mediate the relationship between trait mindfulness and subjective wellbeing (β = 0.078, p = 0.032). In addition, emotional intelligence and self-efficacy played a sequential mediating role between trait mindfulness and subjective wellbeing (β = 0.072, p = 0.005). This study revealed the relationship between kindergarten teachers' trait mindfulness and subjective wellbeing through structural equation modeling and understood its role path, enriching the research on the Chinese preschool teachers in the field, and providing a literature reference for the international community to understand the Chinese kindergarten teachers. At the same time, the study also has some limitations, such as the use of a cross-sectional design method, a relatively single method, and the impact of COVID-19. However, we believe that this study will further enrich the research literature on the relationship between trait mindfulness and subjective wellbeing of Chinese kindergarten teachers.


Bioequivalence of an ezetimibe/simvastatin combination tablet and coadministration of ezetimibe and simvastatin as separate tablets in healthy subjects.
To assess the bioequivalence of an ezetimibe/simvastatin (EZE/SIMVA) combination tablet compared to the coadministration of ezetimibe and simvastatin as separate tablets (EZE + SIMVA). In this open-label, randomized, 2-part, 2-period crossover study, 96 healthy subjects were randomly assigned to participate in each part of the study (Part I or II), with each part consisting of 2 single-dose treatment periods separated by a 14-day washout. Part I consisted of Treatments A (EZE 10 mg + SIMVA 10 mg) and B (EZE/SIMVA 10/10 mg/mg) and Part II consisted of Treatments C (EZE 10 mg + SIMVA 80 mg) and D (EZE/SIMVA 10/80 mg/mg). Blood samples were collected up to 96 hours post-dose for determination of ezetimibe, total ezetimibe (ezetimibe + ezetimibe glucuronide), simvastatin and simvastatin acid (the most prevalent active metabolite of simvastatin) concentrations. Ezetimibe and simvastatin acid AUC(0-last) were predefined as primary endpoints and ezetimibe and simvastatin acid Cmax were secondary endpoints. Bioequivalence was achieved if 90% confidence intervals (CI) for the geometric mean ratios (GMR) (single tablet/coadministration) of AUC(0-last) and Cmax fell within prespecified bounds of (0.80, 1.25). The GMRs of the AUC(0-last) and Cmax for ezetimibe and simvastatin acid fell within the bioequivalence limits (0.80, 1.25). EZE/ SIMVA and EZE + SIMVA were generally well tolerated. The lowest and highest dosage strengths of EZE/SIMVA tablet were bioequivalent to the individual drug components administered together. Given the exact weight multiples of the EZE/SIMVA tablet and linear pharmacokinetics of simvastatin across the marketed dose range, bioequivalence of the intermediate tablet strengths (EZE/SIMVA 10/20 mg/mg and EZE/SIMVA 10/40 mg/mg) was inferred, although these dosages were not tested directly. These results indicate that the safety and efficacy profile of EZE + SIMVA coadministration therapy can be applied to treatment with the EZE/SIMVA tablet across the clinical dose range.


Micronuclei and other nuclear lesions as genotoxicity indicators in rainbow trout Oncorhynchus mykiss.
The induction of micronuclei and other nuclear abnormalities in renal erythrocytes of rainbow trout Oncorhynchus mykiss by six genotoxic compounds is evaluated. Colchicine, mitomycin, cyclophosphamide, acrylamide, methyl-methanesulfonate, and N-ethyl-N-nitrosourea were intraperitoneally injected in trout. Our results show that cyclophosphamide induces the formation of micronuclei and also the other nuclear abnormalities; N-ethyl-N-nitrosourea, acrylamide, and colchicine induce only micronuclei; mitomycin-C induces only other nuclear abnormalities but not micronuclei. Methyl-methanesulfonate does not induce nuclear abnormalities in rainbow trout at the dose assayed in this work. The possible genotoxic origin for the different nuclear abnormalities is discussed.


Radiographic assessment of instability of the knee due to rupture of the anterior cruciate ligament. A quadriceps-contraction technique.
We compared the results of a radiographic technique for the measurement of instability of the knee with those obtained with a KT-1000 arthrometer. The study was conducted on both knees of sixty patients who had a ruptured anterior-cruciate ligament in one knee, as well as in ten control subjects. The radiographic technique included the examination of a true lateral radiograph, made while the knee was in full extension and the quadriceps was maximally contracted, with a 66.7-newton downward force produced by a 6.8-kilogram weight suspended from the ankle. As demonstrated by both techniques, the maximum difference between the displacements of the right and left knees in the control subjects was 2.5 millimeters and the mean difference between the displacements in the two knees in the patients was 7.5 millimeters. In fourteen of the sixty knees in which the ligament was ruptured, the injury was acute. The forward translation of the medial side in these fourteen knees was compared with that in the forty-six knees in which the injury was chronic. The mean difference in the displacement of the medial side in the right and left knees was 3.5 millimeters in the fourteen patients who had an acute injury and 5.0 millimeters in the forty-six patients who had a chronic injury. Thirteen of the sixty patients had disruption of the posteromedial corner of the injured knee, and the translation of the medial side in these knees was significantly increased compared with that in the intact knees of the same patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Borderless teleradiology with CHILI.
Teleradiology is one of the most evolved areas of telemedicine, but one of the basic problems which remains unsolved concerns system compatibility. The DICOM (Digital Imaging and Communications in Medicine) standard is a prerequisite, but it is not sufficient in all aspects. Examples of other currently open issues are security and cooperative work in synchronous teleconferences. Users without a DICOM radiological workstation would benefit from the ability to join a teleradiology network without any special tools. Drawbacks of many teleradiology systems are that they are monolithic in their software design and cannot be adapted to the actual user's environment. Existing radiological systems currently cannot be extended with additional software components. Consequently, every new application usually needs a new workstation with a different look and feel, which must be connected and integrated into the existing infrastructure. This paper introduces the second generation teleradiology system CHILI. The system has been designed to match both the teleradiology requirements of the American College of Radiology (ACR), and the functionality and usability needs of the users. The experiences of software developers and teleradiology users who participated in the first years of the clinical use of CHILI's predecessor MEDICUS have been integrated into a new design. The system has been designed as a component-based architecture. The most powerful communication protocol for data exchange and teleconferencing is the CHILI protocol, which includes a strong data security concept. The system offers, in addition to its own secure protocol, several different communication Methods: DICOM, classic e-mail, Remote Copy functions (RCP), File Transfer Protocol (FTP), the internet protocols HTTP (HyperText Transfer Protocol) and HTTPS (HyperText Transfer Protocol Secure),and CD-ROMs for off-line communication. These transfer METHODS allow the user to send images to nearly anyone with a computer and a network. The drawbacks of the non-CHILI protocols are that teleconferences are not possible, and that the user must take reasonable precautions for data privacy and security. The CHILI PlugIn mechanism enables the users or third parties to extend the system capabilities by adding powerful image postprocessing functions or interfaces to other information systems. Suitable PlugIns can be either existing programs, or dedicated applications programmed with interfaces to the CHILI components. The developer may freely choose programming languages and interface toolkits. The CHILI architecture is a powerful and flexible environment for Picture Archiving and Communications Systems (PACS)and teleradiology. More than 40 systems are currently running in clinical routine in Germany. More than 300,000 images have been distributed among the communication partners in the last two years. Feedback and suggestions from the users influenced the system architecture by a great extent. The proposed and implemented system has been optimized to be as platform independent, open, and secure as possible.


SwissBioPics-an interactive library of cell images for the visualization of subcellular location data.
SwissBioPics (www.swissbiopics.org) is a freely available resource of interactive, high-resolution cell images designed for the visualization of subcellular location data. SwissBioPics provides images describing cell types from all kingdoms of life-from the specialized muscle, neuronal and epithelial cells of animals, to the rods, cocci, clubs and spirals of prokaryotes. All cell images in SwissBioPics are drawn in Scalable Vector Graphics (SVG), with each subcellular location tagged with a unique identifier from the controlled vocabulary of subcellular locations and organelles of UniProt (https://www.uniprot.org/locations/). Users can search and explore SwissBioPics cell images through our website, which provides a platform for users to learn more about how cells are organized. A web component allows developers to embed SwissBioPics images in their own websites, using the associated JavaScript and a styling template, and to highlight subcellular locations and organelles by simply providing the web component with the appropriate identifier(s) from the UniProt-controlled vocabulary or the 'Cellular Component' branch of the Gene Ontology (www.geneontology.org), as well as an organism identifier from the National Center for Biotechnology Information taxonomy (https://www.ncbi.nlm.nih.gov/taxonomy). The UniProt website now uses SwissBioPics to visualize the subcellular locations and organelles where proteins function. SwissBioPics is freely available for anyone to use under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. www.swissbiopics.org.


The relations of alcohol and the cardiovascular system.
The effects of alcohol on heart muscle have been explored in numerous studies of normal and diseased humans, intact animals, and isolated animal heart muscle preparations. The results vary according to dose, route, duration, and frequency of administration, parameters measured, and pathologic state of subjects. Most studies indicate that alcohol in sufficient doses decreases myocardial contractility. The dose required for this effect in humans may be lower if there is clinical evidence of heart muscle disease or if the subject has ingested substantial amounts of alcohol for a long time.


Increased live birth rates with GnRH agonist addition for luteal support in ICSI/IVF cycles: a systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to evaluate whether the addition of GnRH agonist for luteal support in ICSI/IVF cycles enhances the probability of live birth. Systematic literature search (MEDLINE, EMBASE, CENTRAL and RCT registries) was conducted to identify relevant randomized controlled trials published as full manuscripts. Meta-analysis of data yielded pooled risk differences (RDs) and 95% confidence intervals (CIs). A random effects model was applied for pooling the studies. Six relevant RCTs were identified including a total of 2012 patients. The probability of live birth rate (RD: +16%, 95% CI: +10 to +22%) was significantly higher in patients who received GnRH agonist support compared with those who did not. The subgroup analysis according to the type of GnRH analogue used for LH suppression did not change the effect observed (studies in which GnRH agonist was used during ovarian stimulation, RD: +15%, 95% CI: +5 to +23%); (studies in which GnRH antagonist was used during ovarian stimulation, RD: +19%, 95% CI: +11 to +27%). The best available evidence suggests that GnRH agonist addition during the luteal phase significantly increases the probability of live birth rates.


Acid phosphatase and leucine aminopeptidase activity in the uterine flushings of non-pregnant and pregnant gilts.
The activities of uteroferrin, measured as acid phosphatase (AP), and an aminoacylpeptidase (AA) were measured in uterine flushings collected from gilts on Days 6, 8, 10, 12, 14, 15, 16 and 18 of the oestrous cycle and pregnancy (N = 37). Changes in AP (P less than 0.05) were associated with day for both specific and total AP in non-pregnant and pregnant gilts. For pregnant and non-pregnant gilts, AP activity was greatest between Days 14 and 16 and then decreased to Day 18. The AA specific activity increased (P less than 0.01) between Days 10 and 12 of the oestrous cycle and pregnancy, but neither effects of pregnancy nor day by pregnancy status interaction were detected. The AA total activity was greater for pregnant gilts (P less than 0.01). These data suggest an inhibitory effect of oestrogens of blastocyst origin on synthesis and/or secretion of uteroferrin, but not AA.


Non-linear hierarchy of the quorum sensing signalling pathway in bloodstream form African trypanosomes.
Trypanosoma brucei, the agents of African trypanosomiasis, undergo density-dependent differentiation in the mammalian bloodstream to prepare for transmission by tsetse flies. This involves the generation of cell-cycle arrested, quiescent, stumpy forms from proliferative slender forms. The signalling pathway responsible for the quorum sensing response has been catalogued using a genome-wide selective screen, providing a compendium of signalling protein kinases phosphatases, RNA binding proteins and hypothetical proteins. However, the ordering of these components is unknown. To piece together these components to provide a description of how stumpy formation arises we have used an extragenic suppression approach. This exploited a combinatorial gene knockout and overexpression strategy to assess whether the loss of developmental competence in null mutants of pathway components could be compensated by ectopic expression of other components. We have created null mutants for three genes in the stumpy induction factor signalling pathway (RBP7, YAK, MEKK1) and evaluated complementation by expression of RBP7, NEK17, PP1-6, or inducible gene silencing of the proposed differentiation inhibitor TbTOR4. This indicated that the signalling pathway is non-linear. Phosphoproteomic analysis focused on one pathway component, a putative MEKK, identified molecules with altered expression and phosphorylation profiles in MEKK1 null mutants, including another component in the pathway, NEK17. Our data provide a first molecular dissection of multiple components in a signal transduction cascade in trypanosomes.


Do Mothers with Lower Socioeconomic Status Contribute to the Rate of All-Cause Child Mortality in Kazakhstan?
This study aimed to explore whether or not mothers with higher educational and wealth status report lower rate of child mortality compared to those with less advantageous socioeconomic situation. Data used were cross-sectional and collected from Multiple Indicator Cluster Survey in Kazakhstan conducted in 2015. Subjects experiencing childbirth were 9278 women aging between 15 and 49 years. The associations between maternal education and household wealth status with child mortality were examined by multivariate analytical methods. The overall prevalence of child mortality was 6.7%, with noticeable variations across the different regions. Compared with women who had the highest educational status, those with upper and lower secondary were 1.47 and 1.89 times more likely to experience child death. Women in the lowest and second lowest wealth quintile had 2.74 and 2.68 times higher odds of experiencing child death compared with those in the richest wealth status households. Policy makers pay special attention to improving socioeconomic status of the mothers in an effort to reduce child mortality in the country. Women living in the disadvantaged regions with poor access to quality health care services should be regarded as a top priority.


Surface plasmon coupling effects on the photon color conversion behaviors of colloidal quantum dots in a GaN nanoscale hole with a nearby quantum-well structure.
To improve color conversion performance for color display application, we study the near-field-induced nanoscale-cavity effects on the emission efficiency and Förster resonance energy transfer (FRET) under the condition of surface plasmon (SP) coupling by inserting colloidal quantum dots (QDs) and synthesized Ag nanoparticles (NPs) into surface nano-holes fabricated on a GaN template and an InGaN/GaN quantum-well (QW) template. In the QW template, the inserted Ag NPs are close to either QWs or QDs for producing three-body SP coupling to enhance color conversion. Time-resolved and continuous-wave photoluminescence (PL) behaviors of the QW- and QD-emitting lights are investigated. The comparison between the nano-hole samples and the reference samples of surface QD/Ag NP shows that the nanoscale-cavity effect of the nano-hole leads to the enhancements of QD emission, FRET between QDs, and FRET from QW into QD. The SP coupling induced by the inserted Ag NPs can enhance the QD emission and FRET from QW into QD. Its result is further enhanced through the nanoscale-cavity effect. The relative continuous-wave PL intensities among different color components also show the similar behaviors. By introducing SP coupling to a color conversion device with the FRET process in a nanoscale cavity structure, we can significantly improve the color conversion efficiency. Simulation results confirm the basic observations in experiment.


Retrospective study evaluation of DGGR lipase for diagnosis, agreement with pancreatic lipase and prognosis in dogs with suspected acute pancreatitis.
Activity of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase is considered to be more pancreas specific than traditional lipase assays. The aim of this study was to evaluate the diagnostic performance of DGGR lipase activity for suspected acute pancreatitis in dogs and to assess its prognostic usefulness. Retrospective study of case records for suspected acute pancreatitis based on clinician-stated diagnosis, point-of-care and quantitative canine pancreas-specific lipase (cPL) results and consistent ultrasonographic features. Diagnostic performance of DGGR lipase was assessed by receiver-operating characteristic curve analysis, agreement by Cohen's kappa (κ) and prognostic value by multiple regression analysis. Median DGGR lipase activity was significantly (P < 0.001) higher in dogs with suspected acute pancreatitis [93.7 (range, 11.0-2853.0) U/L (n = 158)] compared to those with no evidence of pancreatitis [range, 20.9 (6.7-89.0) U/L (n = 356)]. A DGGR lipase activity >42.15 U/L had the best combined diagnostic sensitivity (81.0%) and specificity (92.1%). Previously established cut-offs (>130 and >80 U/L) had sensitivities of 40.5 and 43.0%, and specificities of 100 and 99.7%, respectively. There was near perfect (κ = 0.821) and substantial (κ = 0.751) agreement between DGGR lipase activity >42.15 U/L and quantitative cPL concentrations ≥200 and ≥400 μg/L, respectively. DGGR lipase activity but not quantitative cPL concentration was statistically (P = 0.043, odds ratio = 0.999) predictive of discharge but clinical utility is questionable. Using DGGR lipase at the lower cut-off could provide an additional test for supporting a diagnosis of acute pancreatitis in dogs particularly if cPL results are not available. Larger studies are required to more fully assess its value in prognostication.


The impact of respiratory motion on tumor quantification and delineation in static PET/CT imaging.
Our aim is to investigate the impact of respiratory motion on tumor quantification and delineation in static PET/CT imaging using a population of patient respiratory traces. A total of 1295 respiratory traces acquired during whole body PET/CT imaging were classified into three types according to the qualitative shape of their signal histograms. Each trace was scaled to three diaphragm motion amplitudes (6 mm, 11 mm and 16 mm) to drive a whole body PET/CT computer simulation that was validated with a physical phantom experiment. Three lung lesions and one liver lesion were simulated with diameters of 1 cm and 2 cm. PET data were reconstructed using the OS-EM algorithm with attenuation correction using CT images at the end-expiration phase and respiratory-averaged CT. The errors of the lesion maximum standardized uptake values (SUV(max)) and lesion volumes between motion-free and motion-blurred PET/CT images were measured and analyzed. For respiration with 11 mm diaphragm motion and larger quiescent period fraction, respiratory motion can cause a mean lesion SUV(max) underestimation of 28% and a mean lesion volume overestimation of 130% in PET/CT images with 1 cm lesions. The errors of lesion SUV(max) and volume are larger for patient traces with larger motion amplitudes. Smaller lesions are more sensitive to respiratory motion than larger lesions for the same motion amplitude. Patient respiratory traces with relatively larger quiescent period fraction yield results less subject to respiratory motion than traces with long-term amplitude variability. Mismatched attenuation correction due to respiratory motion can cause SUV(max) overestimation for lesions in the lower lung region close to the liver dome. Using respiratory-averaged CT for attenuation correction yields smaller mismatch errors than those using end-expiration CT. Respiratory motion can have a significant impact on static oncological PET/CT imaging where SUV and/or volume measurements are important. The impact is highly dependent upon motion amplitude, lesion location and size, attenuation map and respiratory pattern. To overcome the motion effect, motion compensation techniques may be necessary in clinical practice to improve the tumor quantification for determining the response to therapy or for radiation treatment planning.


Characterization of LAG-3, CTLA-4, and CD8+ TIL density and their joint influence on the prognosis of patients with esophageal squamous cell carcinoma.
We aimed to characterize the relationships of lymphocyte activation gene-3 (LAG-3) expression, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) expression, and CD8+ tumor-infiltrating lymphocyte (TIL) density, and to investigate the joint prognostic impact of these three markers in patients with surgically resected esophageal squamous cell carcinoma (ESCC). Expression of LAG-3, CTLA-4 and the density of CD8+ TILs were evaluated by immunohistochemistry in resected ESCC. The associations between LAG-3 expression and clinicopathologic characteristics, as well as patient prognoses, were analyzed. A total of 183 patients were included. LAG-3 expression was observed in 69 (37.7%) patients. Positive LAG-3 expression was significantly associated with CTLA-4 expression (P=0.004). LAG-3 positivity, CTLA-4 positivity, and low CD8+ TIL densities were significantly associated with worsening recurrence-free survival (RFS) [LAG-3: hazard ratio (HR), 1.72; 95% confidence interval (CI), 1.10-2.89; P=0.019; CTLA-4: HR, 1.69; 95% CI, 1.04-2.73; P=0.033; CD8+: HR, 0.60; 95% CI, 0.38-0.94; P=0.025] and overall survival (OS) (LAG-3: HR, 2.09; 95% CI, 1.24-3.53; P=0.006; CTLA-4: HR, 1.47; 95% CI, 0.86-2.53; P=0.161; CD8+: HR, 0.56; 95% CI, 0.33-0.95; P=0.032). Subgroup analysis revealed that the LAG-3 CTLA-4 CD8+ group had the best RFS (P<0.001) and OS (P<0.001). LAG-3 expression was correlated with CTLA-4 expression on TILs. Positive LAG-3 expression was associated with poor prognoses in ESCC. A combination of LAG-3, CTLA-4 expression and CD8+ TILs density could further stratify patients into different subgroups with distinct prognoses.


A retrospective database study of oral corticosteroid and bisphosphonate prescribing patterns in England.
Exposure to oral corticosteroids (OCS) is associated with an increased risk of osteoporosis and fragility fractures. Guidelines suggest bisphosphonate (BP) therapy as the first-line treatment of glucocorticoid-induced osteoporosis (GIOP). This population study used publicly available data, including prescription annual cost analysis and monthly practice-level data. Our aim was to examine the prescribing of OCS and BP at practice level and investigate reasons for variation using a mixed-effect negative binomial regression analysis. There was a rise in OCS and BP prescriptions of 55% and 1200% from 1998 to 2018, respectively. Of the 6586 included practices, the median (IQR) of OCS and BP prescriptions were 120.8 (84.8-160.4) and 107.7 (73.8-147.4) per 1000 patients, respectively. Asthma and chronic obstructive pulmonary disease (COPD) were significantly associated with OCS use (p < 0.0001), but only COPD was associated with BP use (p < 0.0001). Higher OCS prescribing rates were associated with higher BP prescribing rates (5th to 1st quintile-IRR = 1.99; 95% CI: 1.88-2.10). Practice list size, deprivation and advanced age were all associated with both drugs (p < 0.0001). In conclusion, although OCS use is positively associated with BP prescription, variation among practices and CCGs exists. The variation in prescribing suggests there is still a need to improve GIOP prevention.


Structural Engineering of Ionic MOF@COF Heterointerface for Exciton-Boosting Sunlight-Driven Photocatalytic Filter.
Sunlight-driven photocatalytic filters against pathogenic bioaerosols have attracted a lot of interest. However, developing an efficient interception system that shows enhanced visible-light harvesting, controllable charge dynamic, and boosted ROS generation remains a grand challenge. Here, we designed an ionic ZIF-8@iCOF nanocomposite as a sunlight-driven photocatalytic filter through elaborate structural engineering of the heterointerface between ZIF-8 and cationic iCOF layers. The photoactive experiments reveal significant improvements in the visible light absorption and sunlight-driven exciton-enhanced intersystem crossing to boost the generation of singlet oxygen (220%) and also obtain antibacterial efficiency of 99.99999% after 15 min irradiation. After combining with commercial polymer, resultant ZIF-8@iCOF/polyacrylonitrile (PAN) fibrous membranes exhibited high interception efficiency for both PM10 and PM2.5 (98%), being close to the commercial N95. This fibrous membrane also possesses good biocompatibility and strong elimination of bacteria under sunlight conditions, satisfying for the long-lasting contact usage. This finding not only showcases the promise of the porous materials-based fibrous membranes for efficient photocatalytic filter against pathogenic bioaerosols but also highlights the importance of accurate structural engineering for the advancement of sunlight-driven photocatalytic systems in environment and energy-related fields.


[Association of Polymorphic Variants of Gene MUC19 with Asthma in Russians According to the Results of a Genome-Wide Study].
Asthma is a heterogeneous multifactorial disease that is characterized in most cases by chronic respiratory tract inflammation. We carried out a GWAS in order to identify susceptibility genes for asthma in individuals of different ethnic backgrounds. The study sample consisted of 358 unrelated patients with asthma (160 Russians, 125 Tatars, and 73 Bashkirs) and 369 individuals of a control group (152 Russians, 117 Tatars, and 100 Bashkirs). DNA samples were genotyped with an Illumina human610 quad array (Illumina) as part of the project GABRIEL. Replication of the results of genome-wide analysis was carried out on an additional independent sample of 310 asthma patients (132 Russians, 105 Tatars, and 73 Bashkirs) and 310 individuals in a control group (131 Russians, 106 Tatars, and Bashkirs 77). Genome-wide analysis showed an association of asthma in Russians with the polymorphic loci of gene MUC19 (12q12) encoding gel-forming mucin 19. The highest level of association with asthma was found in rs2933346, which is located in intron 52 of this gene (p = 2.59 x 10(-6)). Seven polymorphic loci of gene MUC19 (rs1492313, rs2588401, rs2588402, rs2638863, rs2638864, rs1352940, and rs2933373), which are in close linkage disequilibrium among themselves and rs2933346, are associated with asthma with the same p-value (p = 4.96 x 10(-6)). The replicative study of rs1492313 in the independent sample of individuals confirmed the presence of the association of the polymorphic loci of this gene with the development of asthma in Russians. According to our data, the association of polymorphic variants of gene MUC19 with asthma has not been previously identified in any study. Our results indicate the important role of polymorphic variants of gene MUC19 in the formation of a predisposition to the development of asthma in individuals of Russian ethnicity.


An environmental androgen, 17beta-trenbolone, affects delayed-type hypersensitivity and reproductive tissues in male mice.
Recently, a growth promoter for farm animals, trenbolone acetate, was identified as an environmental androgen that potentially affects reproduction. Because androgens also suppress immunity, it was hypothesized that an active metabolite of trenbolone acetate, 17beta-trenbolone (TB), might impair immune responses. Castrated adult CD-1 mice were injected daily with either one of two different doses of 17beta-trenbolone (TB), testosterone propionate (TP), or corn oil (vehicle). The antigen-specific immune response was assessed by measuring delayed-type hypersensitivity (DTH) responses. Reproductive response was assessed by measuring reproductive tissue mass and determining testosterone concentrations. Mice treated with TB or TP displayed larger reproductive tissue mass than males treated with corn oil. Furthermore, males exposed to the highest dose of TB displayed a reduced DTH response compared to vehicle-treated animals. In comparison, TP, at a similar dose, only minimally reduced the DTH response. These data support the reproductive and potentially immunosuppressive effects of this environmental androgen, and raise the possibility of health concerns for individuals or populations in contact with high concentrations of TB.


CoSeg: Cognitively Inspired Unsupervised Generic Event Segmentation.
Some cognitive research has discovered that humans accomplish event segmentation as a side effect of event anticipation. Inspired by this discovery, we propose a simple yet effective end-to-end self-supervised learning framework for event segmentation/boundary detection. Unlike the mainstream clustering-based methods, our framework exploits a transformer-based feature reconstruction scheme to detect event boundaries by reconstruction errors. This is consistent with the fact that humans spot new events by leveraging the deviation between their prediction and what is perceived. Thanks to their heterogeneity in semantics, the frames at boundaries are difficult to be reconstructed (generally with large reconstruction errors), which is favorable for event boundary detection. In addition, since the reconstruction occurs on the semantic feature level instead of the pixel level, we develop a temporal contrastive feature embedding (TCFE) module to learn the semantic visual representation for frame feature reconstruction (FFR). This procedure is like humans building up experiences with "long-term memory." The goal of our work is to segment generic events rather than localize some specific ones. We focus on achieving accurate event boundaries. As a result, we adopt the F1 score (Precision/Recall) as our primary evaluation metric for a fair comparison with previous approaches. Meanwhile, we also calculate the conventional frame-based mean over frames (MoF) and intersection over union (IoU) metric. We thoroughly benchmark our work on four publicly available datasets and demonstrate much better results. The source code is available at https://github.com/wang3702/CoSeg.


Evaluation of the prebiotic effects of citrus pectin hydrolysate.
Citrus pectin enzyme hydrolysate (PEH) of different hydrolysis time intervals (6 hours, PEH-6; 12 hours, PEH-12; 24 hours, PEH-24; or 48 hours, PEH-48) or concentrations (1%, 2%, and 4%) was tested for its growth stimulation effect on two probiotics, Bifidobacterium bifidum and Lactobacillus acidophilus. Higher monosaccharide concentrations and smaller molecular weights of PEHs were obtained by prolonging the hydrolysis time. In addition, higher PEH concentrations resulted in significantly higher (p < 0.05) probiotic populations, pH reduction, and increase in total titratable acidity than the glucose-free MRS negative control. Furthermore, significantly higher populations in the low pH environment and longer survival time in nonfat milk (p < 0.05) were observed when the two probiotics were incubated in media supplemented with 2% PEH-24, than in glucose and the negative control. In comparison with other prebiotics, addition of 2% PEH-24 resulted in a more significant increase in the probiotic population (p < 0.05) than in the commercial prebiotics. This study demonstrated that PEH derived from citrus pectin could be an effective prebiotic to enhance the growth, fermentation, acid tolerance, and survival in nonfat milk for the tested probiotics.


Scalloping Characteristics in a Patient with Extra-Cranial Hemangioma.
Infantile hemangiomas are the most common benign tumors of infancy and childhood with a reported incidence of 4% to 10% in infants. We report of a 9 year-old male child with a history of progressively increasing swelling over the right eyebrow region. The lesion was present since childhood; however, it increased in in size over the previous 3-4 months. The CT scan showed scalloping over the right supra-orbital ridge with an intact bone. The child underwent total excision of the lesion. A characteristic scalloping seen on imaging (depression in the outer or inner table of the skull) can help differentiate lesions of extracranial and intracranial origins.


Exploring the accuracy and usefulness of semi-empirically scaled ADC schemes by blending second and third order terms.
Different approaches to mixed-order algebraic-diagrammatic construction (ADC) schemes are investigated. The performance of two different strategies for scaling third-order contributions to the ADC secular matrix is evaluated. Both considered schemes employ a single tuning parameter and conserve general properties inherent to all ADC methods, such as hermiticity and size-consistency. The first approach, scaled-matrix ADC[(2) + x(3)], scales all contributions first occurring in ADC(3) equally and leads to an improvement of the accuracy of excitation energies compared to ADC(3) for x = 0.4-0.5. However, with respect to excited state dipole moments, this method provides lower accuracy than ADC(3). The second scaling approach, MP[(1) + x(2)] - ISR(3), scales the second order contributions of the ground-state wavefunction and derives a rigorous ADC scheme via the intermediate state representation formalism. Although the error in excitation energies is not improved, this method provides insight into the relevance of the individual terms of the ADC(3) matrix and indicates that the MP(2) wavefunction is, indeed, the optimal reference wavefunction for deriving a third-order single-reference ADC scheme.


Fused Isoindigo Ribbons with Absorption Bands Reaching Near-Infrared.
Through fusing isoindigo (IID) units at 6,7;6',7'-positions, a series of new near-infrared (NIR) absorbing and stable ribbon-like conjugated molecules, namely nIIDs in which n represents the number of IID units, have been synthesized. The optical band gaps of the molecules are lowered from 2.03 eV of 1IID to 1.12 eV of 6IID with the increase of the conjugation length. 3IID, 4IID, and 6IID have strong absorption in the NIR region and exhibit photothermal conversion efficiencies of greater than 50 % under laser irradiation at λ=808 nm.


Emotion Regulation Deficits in Adolescent Girls with Major Depression, Anorexia Nervosa and Comorbid Major Depression and Anorexia Nervosa.
In adolescence, both major depression (MD) and anorexia nervosa (AN) are associated with deficits in emotion regulation (ER). However, studies have yet to compare ER profiles within the disorders and the effect of comorbid MD+AN is unclear. This study examined the habitual use of ER in 229 girls, aged 12-18 years, with MD (n = 84), AN (n = 37), comorbid MD+AN (n = 25), and healthy girls (n = 83). Girls with MD, AN and MD+AN reported more maladaptive and less adaptive ER strategies than healthy girls. MD and MD+AN groups showed more frequent use of maladaptive ER compared to only AN, with no differences between only MD and MD+AN. This suggests that MD+AN is not necessarily associated with higher ER deficits, rather, an additional diagnosis of MD exacerbates impairments in AN. Identifying specific ER profiles can provide important targets in prevention and treatment for AN, MD and AN+MD.


Understanding team adaptation: a conceptual analysis and model.
This endeavor provides a multidisciplinary, multilevel, and multiphasic conceptualization of team adaptation with theoretical roots in the cognitive, human factors, and industrial-organizational psychology literature. Team adaptation and the emergent nature of adaptive team performance are defined from a multilevel, theoretical standpoint. An input-throughput-output model is advanced to illustrate a series of phases unfolding over time that constitute the core processes and emergent states underlying adaptive team performance and contributing to team adaptation. The cross-level mixed-determinants model highlights team adaptation in a nomological network of lawful relations. Testable propositions, practical implications, and directions for further research in this area are also advanced.