[Developing and application of an autoverification system for clinical chemistry and immunology test results].
Objective: To develop and validate an autoverification system for biochemistry and immunology test results for application in routine work. Methods: Algorithms was designed and translated into the laboratory information system. Parameters including verify limit, delta check, logic relation between tests was set up in the system. Verification rate of every test and the causes of fails were analyzed, according to which the system and parameters were modified. The autoverified reports were evaluated by chief technicians. Only when all of the autoverified results pass the evaluation, the system applied for routine work of releasing the results. Autoverification rate and turnaround time(TAT) were calculated for evaluation of the efficiency of the system. Results: A brand new autoverification system was developed and applied for routine work. The autoverification rate for each single test was 91.1%-96.6%. The autoverification rate for reports was 74%. With the autoverification system, the media of TAT reduced from 111.6(53.9-270.7) min to 87.2(45.4-202.4) min, whereas the time from instrument finishing analysis to releasing the reports reduced from 18.6(1.0-99.3) min to 0.1(0-58.3)min. The number of staff specified for results validation reduced from three to one. Conclusions: The newly developed system can be used for autoverification of biochemistry and immunology test results. The autoverification system can greatly reduce TAT and raise working efficiency. It's essential to employ carefully designed algorithm, appropriate parameters and comprehensive evaluation when developing a new autoverification system.


Diffusion quantum Monte Carlo method on diradicals using single- and multi-determinant-Jastrow trial wavefunctions and different orbitals.
In this work, the diffusion quantum Monte Carlo (DMC) method is employed to calculate the energies of singlet and triplet states for a series of organic diradicals and diatomic diradicals with π2 configuration. Single-determinant-Jastrow (SDJ) trial wavefunctions for triplet states, two-determinant-Jastrow (2DJ) trial wavefunctions for the singlet states, and multi-determinant-Jastrow (MDJ) trial wavefunctions are employed in DMC calculations using restricted open-shell B3LYP (ROB3LYP) orbitals, complete-active-space self-consistent field (CASSCF) orbitals, state-average CASSCF orbitals, or frozen-CASSCF orbitals. Our results show that DMC energies using either SDJ/2DJ or MDJ with ROB3LYP orbitals are close to or lower than those with the other orbitals for organic diradicals, while they are not very sensitive to the employed orbitals for diatomic diradicals. Furthermore, using MDJ can reduce DMC energies to some extent for most of the investigated organic diradicals and some diatomic diradicals. The importance of MDJ on DMC energies can be estimated based on the percentage of main determinants in the CASCI wavefunction. On the other hand, singlet-triplet gaps can be calculated reasonably with DMC using MDJ with a mean absolute error of less than 2 kcal/mol with all these orbitals. CASCI wavefunctions using density functional theory orbitals are preferred in constructing MDJ trial wavefunctions in practical DMC calculations since it is easier to obtain such wavefunctions than CASSCF methods.


The role of multiple metabolic genes in predicting the overall survival of colorectal cancer: A study based on TCGA and GEO databases.
The recent advances in gene chip technology have led to the identification of multiple metabolism-related genes that are closely associated with colorectal cancer (CRC). Nevertheless, none of these genes could accurately diagnose or predict CRC. The prognosis of CRC has been made by previous prognostic models constructed by using multiple genes, however, the predictive function of multi-gene prognostic models using metabolic genes for the CRC prognosis remains unexplored. In this study, we used the TCGA-CRC cohort as the test dataset and the GSE39582 cohort as the experimental dataset. Firstly, we constructed a prognostic model using metabolic genes from the TCGA-CRC cohort, which were also associated with CRC prognosis. We analyzed the advantages of the prognostic model in the prognosis of CRC and its regulatory mechanism of the genes associated with the model. Secondly, the outcome of the TCGA-CRC cohort analysis was validated using the GSE39582 cohort. We found that the prognostic model can be employed as an independent prognostic risk factor for estimating the CRC survival rate. Besides, compared with traditional clinical pathology, it can precisely predict CRC prognosis as well. The high-risk group of the prognostic model showed a substantially lower survival rate as compared to the low-risk group. In addition, gene enrichment analysis of metabolic genes showed that genes in the prognostic model are enriched in metabolism and cancer-related pathways, which may explain its underlying mechanism. Our study identified a novel metabolic profile containing 11 genes for prognostic prediction of CRC. The prognostic model may unravel the imbalanced metabolic microenvironment, and it might promote the development of biomarkers for predicting treatment response and streamlining metabolic therapy in CRC.


Important contribution of the novel locus comEB to extracellular DNA-dependent Staphylococcus lugdunensis biofilm formation.
The coagulase-negative species Staphylococcus lugdunensis is an emerging cause of serious and potentially life-threatening infections, such as infective endocarditis. The pathogenesis of these infections is characterized by the ability of S. lugdunensis to form biofilms on either biotic or abiotic surfaces. To elucidate the genetic basis of biofilm formation in S. lugdunensis, we performed transposon (Tn917) mutagenesis. One mutant had a significantly reduced biofilm-forming capacity and carried a Tn917 insertion within the competence gene comEB. Site-directed mutagenesis and subsequent complementation with a functional copy of comEB verified the importance of comEB in biofilm formation. In several bacterial species, natural competence stimulates DNA release via lysis-dependent or -independent mechanisms. Extracellular DNA (eDNA) has been demonstrated to be an important structural component of many bacterial biofilms. Therefore, we quantified the eDNA in the biofilms and found diminished eDNA amounts in the comEB mutant biofilm. High-resolution images and three-dimensional data obtained via confocal laser scanning microscopy (CSLM) visualized the impact of the comEB mutation on biofilm integrity. The comEB mutant did not show reduced expression of autolysin genes, decreased autolytic activities, or increased cell viability, suggesting a cell lysis-independent mechanism of DNA release. Furthermore, reduced amounts of eDNA in the comEB mutant biofilms did not result from elevated levels or activity of the S. lugdunensis thermonuclease NucI. In conclusion, we defined here, for the first time, a role for the competence gene comEB in staphylococcal biofilm formation. Our findings indicate that comEB stimulates biofilm formation via a lysis-independent mechanism of DNA release.


Tissue-specific cell-surface antigens in embryonic cells.
With the use of antisera prepared in rabbits against suspensions of live embryonic chick tissue cells, qualitative differences in cell surface antigens were demonstrated on cells from different embryonic chick tissues by immune agglutination and immunofluorescence. Unabsorbed antisera reacted with both homologous and nonhomologous cells; thorough absorption of the antisera with heterologous tissues removed cross-reacting antibodies, and the antisera acquired a high degree of tissue specificity. Thus, antiretina cell serum absorbed with nonretina cells or tissues, agglutinated only neural retina cells, and was shown by immunofluorescence tests to react specifically with the surface of retina cells, both in cell suspensions and in frozen tissue sections. Comparable results with antisera against cells from embryonic liver and other tissues demonstrated the existence of tissue-specific, phenotypic disparities in the antigenicities of embryonic cell surfaces, in addition to the presence of cell-surface antigens shared by certain classes of cells, and of antigens common to all cells in the embryo. The results are discussed in terms of the possible involvement of such phenotypic determinants in the specification of cell surfaces, in relation to cell recognition and developmental interactions.


A quantum phase gate capable of effectively collecting photons based on a gap plasmon structure.
The realization of a quantum phase gate in micro-nano structures is beneficial to the miniaturization and integration of on-chip quantum circuits. Surface plasmons are well known for ultra-small mode volumes, which can further reduce the size of quantum devices. However, high fidelity quantum phase gates using surface plasmon nanocavities in a strong coupling regime have not been proposed yet. Here, based on a metallic nanocone-nanowire structure, we theoretically demonstrate a quantum phase gate, simultaneously achieving an arbitrary phase shift and effective photon collection at the nanoscale. The gate can reach 88.8% fidelity due to combining the enhanced coupling coefficient achievable by gap plasmons with low cavity loss resulting from gain medium. Meanwhile, emitted photons can be guided via the nanowire with collection efficiency over 30%. The system may act as universal quantum nodes that can process and store quantum information. It also holds promise for the physical implementation of on-chip multifunctional quantum gates and novel quantum circuits.


Reversible hearing loss after meningitis. Prospective assessment using auditory evoked responses.
Hearing loss (HL) was prospectively studied in 236 children with meningitis using brainstem auditory evoked responses. Hearing loss was detected in 38 (16.1%) in the acute phase of the disease and in 10 (5.2%) of 193 patients who were tested 6 months later. Hearing loss was more frequent and more severe in patients with bacterial meningitis (25.4% in the acute phase, and 8% 6 months later) than in patients with viral and tuberculous meningitis. In half of the affected cases the auditory lesion was bilateral. Follow-up was possible in 32 patients with early postmeningitic HL. Ten (31.2%) had permanent HL while the remaining 22 (68.7%) recovered normal hearing. Severe initial losses tended to be permanent, whereas minimal and intermediate losses were generally reversible and patients recovered completely in 1 to 6 months. The high incidence of HL in bacterial meningitis suggests that any one of the existing methods of auditory screening should be performed in all patients during the convalescent period.


Confinement of nonneutral plasmas on magnetic surfaces.
The confinement of a nonneutral plasma in a magnetic-surface, or stellarator, configuration is explored. The fluid equilibrium equations are derived and are found to be fundamentally different from previous results. Diocotron modes are predicted to be stable. The collisional confinement time can be very long. Possible applications include positron trapping and confinement of positron-electron plasmas. The basic physics can be addressed experimentally in the simple tabletop stellarator planned for construction at Columbia University.


Perinatal mortality in rural India: a strategy for reduction through primary care. I Stillbirths.
In a prospective community based study of the distribution and determinants of stillbirths in a rural area of Maharashtra, India, that was carried out for two years, 3129 singleton and 22 twin births were recorded in a population of 47 000. Of the 3173 babies, 85 singletons and five of the twins were stillborn giving a stillbirth rate of 28.4/1000 births. The causes of stillbirths are analysed and the possibility of reducing the unacceptably high stillbirth rate by adequate training of grassroot level workers in screening pregnant women for detection of "at risk" mothers and their timely referral is discussed.


Self-organized criticality: robustness of scaling exponents.
We investigate a deterministic, conservative, undirected, critical height sandpile model with dissipation of an energy at boundaries that can simulate avalanche dynamics. It was derived from the Bak-Tang-Wiesenfeld model [P. Bak, C. Tang, and K. Wiesenfeld, Phys. Rev. Lett. 59, 381 (1987)] introducing an additional second-higher threshold so the model has two distinct thresholds. Our computer simulations for a two-dimensional lattice show that scaling properties of the model depend on the higher-threshold values and site concentrations. These results are not therefore consistent with the present self-organized criticality hypothesis where the scaling properties are independent of the model parameters.


Sentinel node navigation surgery in early-stage esophageal cancer.
The sentinel node (SN) concept has revolutionized the surgical staging of both melanoma and breast cancer over the past two decades. However, the validity of the SN hypothesis has been controversial for esophageal cancer, because SN mapping for esophageal cancer is technically complicated, and the number of early-stage esophageal cancer is very limited. Nevertheless previous studies nicely demonstrated that SN mapping may be feasible in patients with early-stage esophageal cancer. Transthoracic extended esophagectomy with three-field radical lymph node dissection has been recognized as a curative procedure for thoracic esophageal cancer in Japan. However, uniform application of this highly invasive procedure might increase the morbidity and markedly reduce the quality of life (QOL) after surgery. Although further accumulation of evidence based on multicenter clinical trials using a standard protocol is needed, SN mapping and SN navigation surgery would provide significant information to perform individualized selective lymphadenectomy which might reduce the morbidity and retain the patients' QOL. In addition, technical innovation including the development of new tracers is expected to confirm the accuracy and reliability of SN mapping in esophageal cancer.


Fluorium-Initiated Dealkylative Cyanation of Thioethers to Thiocyanates.
Thioethers are converted to thiocyanates via fluorium-initiated dealkylative cyanation. Selectfluor is used as the oxidant, and trimethylsilyl cyanide is used as the cyanation reagent. The well-streamlined procedure is user-friendly, operationally simple, and step-economical. The current mechanistic studies show that the sulfur radical cation and cyano radical are both involved. They combine to deliver cyanosulfonium, an intermediate toward thiocyanate after dealkylation. Alternatively, a nucleophilic mechanism is also possible. Our dealkyaltive cyanation is also efficient in synthesizing thiocyanates with strongly electrophilic functionalities.


Upregulated Fibulin-1 Increased Endometrial Stromal Cell Viability and Migration by Repressing EFEMP1-Dependent Ferroptosis in Endometriosis.
Endometriosis (EMS) is a prevalent disease in women characterized by the presence of endometrial stroma and glands outside the uterus. Recent studies have showed that EMS is correlated with the resistance of endometrial stromal cells (ESCs) to ferroptosis, an iron-dependent nonapoptotic cell death. Fibulin-1 (FBLN1) is a newly identified target regulated by progesterone in the process of ESC decidualization. However, the role of FBLN1 in regulating ESC ferroptosis and EMS remains unclear. In the present study, the gene expression profiles of GSE58178, GSE23339, and GSE25628 were downloaded from the Gene Expression Omnibus (GEO) database, and the commonly differential genes were identified using Venn diagram analysis. The role of FBLN1 in ESC viability and migration was evaluated using Cell Counting Kit-8, transwell, and western blot analysis. We found that the FBLN1 expression was increased significantly in eutopic and ectopic endometrial tissues of patients with EMS compared with normal endometrium. FBLN1 overexpression in normal ESCs (NESCs) promoted cell viability and migration, whereas FBLN1 inhibition in ectopic ESCs (EESCs) decreased cell viability and migration. Furthermore, FBLN1 inhibition facilitated EESC death by triggering ferroptosis, as evidenced by increased Fe2+, lipid ROS, and malondialdehyde (MDA) level and decreased glutathione peroxidase 4 (GPX4) expression and glutathione (GSH) level. Mechanistically, FBLN1 interacted with EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) and increased the protein stability of EFEMP1. More importantly, EFEMP1 silencing repressed the effect of FBLN1 on regulating EESC ferroptosis, death, and migration. Taken together, these results verify the role of the FBLN1/EFEMP1/ferroptosis pathway in the pathogenesis of EMS, and silencing of FBLN1/EFEMP1 might be an effective approach to treat EMS.


Conformational and electronic engineering of twisted diphenylacetylenes.
[structure: see text] Three tethered diphenylacetylene derivatives were prepared by alkyne metathesis. In these cycles, the twist angle between the two benzene rings is variable and determined by the nature of the linker. The engineering of the twist angle leads to a change of the UV-vis spectra of the cycles. The larger the twist angle in the macrocycles, the more blue shifted their lambda(max) (UV-vis), the lower their fluorescence quantum yield, and the lower field shifted their (13)C NMR signals of the alkyne carbons are.


"Think" versus "feel" framing effects in persuasion.
Three studies explored think ("I think . . . ") versus feel ("I feel . . . ") message framing effects on persuasion.The authors propose a matching hypothesis, suggesting that think framing will be more persuasive when the target attitude or message recipient is cognitively oriented, whereas feel framing will be more persuasive when the target attitude or message recipient is affectively oriented. Study 1 presented cognitively and affectively oriented individuals with a think- or feel-framed message. Study 2 primed cognitive or affective orientation and then presented a think- or feel-framed message. Study 3 presented male and female participants with an advertisement containing think- or feel-framed arguments. Results indicated that think (feel) framing was more persuasive when the target attitude or recipient was cognitively (affectively) oriented. Moreover, Study 2 demonstrated that this matching effect was mediated by processing fluency. Theoretical and practical implications are discussed.


[Securing food quality for consumer protection].
Ensuring the perfect wholesomeness and impeccable quality of foodstuffs in general and foods of animal origin, in particular, starting from their very production via any further processing and handling to their marketing in the retail trade, is also among the tasks incumbent on the veterinarian. Against the backdrop of the completion of the European Single Market, numerous veterinary professional directives were adopted in the best interest of consumer protection and the free movement of foods of animal origin. These directives concern both general inspection provisions and specific sanitary requirements covering the handling of myriad foods of animal origin such as meat, meat products, poultry meat, milk, fish and fish products. This development spawned novel tasks which the official veterinarians, in particular, but also veterinary surgeons, have to take care of. Hence, it is bound to have some impacts on veterinary training as well as on further and in-service training.


Separating true positive predicted residue contacts from false positive ones in mainly alpha proteins, using constrained Metropolis MC simulations.
We present a method that significantly improves the accuracy of predicted proximal residue pairs in protein molecules. Computational methods for predicting pairs of amino acids that are distant in the protein sequence but close in the protein 3D structure can benefit attempts to in silico recognize the fold of a protein molecule. Unfortunately, currently available methods suffer from low predictive accuracy. In this work, we use Monte Carlo simulations to fold protein molecules with proximal pair predictions used as additional energy constraints. To test our methods, we study molecules with known tertiary structures. With Monte Carlo, we generate ensembles of structures for each set of residues constraints. The distribution of the root mean square deviation of the folded structures from the known native structure reveals clear information about the accuracy of the constraint sets used. With recursive substitutions of constraints, false positive predictions are identified and filtered out and significant improvements in accuracy are observed.


Vectors for expression and amplification of cDNA in mammalian cells: expression of rat phenylalanine hydroxylase.
We have constructed two recombinant plasmid vectors for direct expression and amplification of cDNA in mammalian cells. Each vector carries two dominant selectable markers (the bacterial neo gene and the mouse DHFR gene), a promoter sequence (viral LTR in pAV009/A+, and sheep metallothionein promoter in pMT010/A+), a polyadenylation signal sequence, and a Bam HI site to allow insertion of cDNA. We have used these vectors to prepare recombinant clones for the expression of rat phenylalanine hydroxylase (PH) in LTK- cells. Selection of transformants with neomycin followed by selection of the transformants in methotrexate led to a 30- to 60-fold amplification of the DHFR marker and co-amplification of the PH cDNA, with a corresponding increase in the level of PH mRNA and enzyme polypeptide. The expressed enzyme has a subunit molecular weight of 50,000 which corresponds to the W- allele of rat liver PH. PH activity was detected in the transfected cells by enzymatic measurement of the conversion of [14C]phenylalanine to [14C]tyrosine, and by growth of these cells in a tyrosine-free culture medium. Expression of rat PH in cell culture should facilitate the analysis of the biochemical properties of this enzyme.


Renal transplantation in patients with primary immunoglobulin A nephropathy.
Opinions on the clinical course and outcome of renal transplantation in patients with primary immunoglobulin A nephropathy (IgAN) have been controversial. We conducted a retrospective single-centre study on 542 kidney transplant recipients over the period 1984-2001. Long-term outcome and factors affecting recurrence in recipients with primary IgAN were analysed. Seventy-five patients (13.8%) had biopsy-proven IgAN as the cause of renal failure, and their mean duration of follow-up after transplantation was 100 +/- 5.8 months. Fourteen (18.7%) of the 75 patients had biopsy-proven recurrent IgAN, diagnosed at 67.7 +/- 11 months after transplantation. The risk of recurrence was not associated with HLA DR4 or B35. Graft failure occurred in five (35.7%) of the 14 patients: three due to IgAN and two due to chronic rejection. Three (4.9%) of the 61 patients without recurrent IgAN had graft failure, all due to chronic rejection. Graft survival was similar between living-related and cadaveric/living-unrelated patients (12-year graft survival, 88 and 72%, respectively, P = 0.616). Renal allograft survival within the first 12 years was better in patients with primary IgAN compared with those with other primary diseases (80 vs 51%, P = 0.001). Thereafter, IgAN patients showed an inferior graft survival (74 vs 97% in non-IgAN patients, P = 0.001). Our data suggested that around one-fifth of patients with primary IgAN developed recurrence by 5 years after transplantation. Recurrent IgA nephropathy in allografts runs an indolent course with favourable outcome in the first 12 years. However, the contribution of recurrent disease to graft loss becomes more significant on long-term follow up.


Effect of Sleep Intervention Programs during Cardiac Rehabilitation on the Sleep Quality of Heart Patients.
In this quasi-experimental study with unequal control group design, 35 individuals participated in the cardiac rehabilitation program as the experimental group and 35 served as the control group. The program included 12 weeks of exercise, 3 sessions per week, 3 sessions of training programs each lasting for 45 minutes, and a special two-session sleep improvement program. Data were collected using the Pittsburgh Sleep Quality Index and analysed with descriptive and inferential statistical methods. There were not any significant differences between the two groups in age, sex, marital status, smoking, and indication for cardiac rehabilitation (P > 0.05). The scores of sleep quality of patients were 9.2 ± 1.58 before and 4.40 ± 1.14 after intervention in the experimental group and 9.02 ± 2.56 before and 7.48 ± 1.86 after intervention in the control group. There was no significant difference between the two groups before intervention (P = 0.73). yet there was a significant difference after intervention (P = 0.0001). In addition, scores of sleep quality of patients were significantly different in the experimental and control groups before and after intervention (P = 0.0001). Findings indicated that the quality of sleep of cardiac patients improved after the sleep intervention program during the cardiac rehabilitation program. Therefore, it is suggested to implement sleep improvement programs for cardiac patient care as an effective, easy, and feasible technique. In addition, it is necessary to pay more attention to the sleep improvement program in cardiac rehabilitation. Trial Registration. The trial was retrospectively registered on https://en.irct.ir/trial/50799 on 14 September 2020 (14.09.2020) with registration number IRCT20140307016870N6.


Effect of divalent ions on the activity of cancer procoagulant.
The effect of calcium (Ca2+), magnesium (Mg2+), manganese (Mn2+), iron (Fe2+), and zinc (Zn2+) on the factor X-activating activity of cancer procoagulant (CP) was studied. Activity of CP was evaluated with a three-stage chromogenic assay (liquid-phase assay, "native" CP) and with an immunocapture enzyme (ICE) assay (solid-phase assay, immobilized CP). In the liquid-phase assay, CP activity was Ca(2+)-dependent, and Mg2+ (5 mM) or Mn2+ (0.01-0.1 mM) could substitute for Ca2+. There was no additive effect of Mg2+ and Ca2+ on the activity of CP. Activity of CP in the liquid-phase assay, in the presence of 7 mM Ca2+, was enhanced by 0.1 mM Mn2+ to about 240% of the activity observed when only Ca2+ was present in the reaction. Zn2+ and Fe2+ did not activate CP in the absence of Ca2+; they inhibited CP activity in a concentration-dependent mode when administered in the presence of Ca2+. The activity of CP evaluated by the solid-phase assay (ICE assay) was neither Ca(2+)-dependent nor was it susceptible to potentiation by Mn2+ administered after CP was bound to IgM. CP exposed to 5 mM Mn2+ before binding to IgM expressed about 85% higher activity than without the presence of Mn2+. When CP was first preincubated with divalent ion and then immunocaptured, the signal generated in the enzyme-linked immunoadsorbent assay by Mn(2+)-containing CP was significantly different (30% greater) than signals generated by CP without Mn2+ or containing different ion. These data suggest that: (1) there is a significant conformational change of the CP molecule that takes place after capturing CP by the monoclonal IgM antibody on the solid surface; (2) the divalent ions are not directly involved in enzyme-substrate interactions in the CP moiety; and (3) the interaction of Mn2+ with CP seems to be different from that of the other divalent ions.


Preparation and evaluation of goose reovirus inactivated vaccine.
Infection with Goose Reovirus (GRV) can cause serious economic losses in the goose breeding industry. In this study, the GRV allantoic fluid was concentrated and used as an antigen in a formalin-inactivated oil-emulsion vaccine. When 6 day-old geese were inoculated, antibodies against GRV became detectable at 6 days post-vaccination, their concentration peaked at 3 weeks. These antibodies were maintained for longer than 2 weeks. As the most susceptible age for GRV infection is birds under 2 weeks of age this vaccine should provide adequate cover for the most at risk birds. When geese were exposed to reovirus at different time intervals after immunization, the data revealed that the vaccine can provide a protection rate of 80%. The developed vaccine has good stability and could be stored at 4 °C for at least 12 months. These results indicate that the developed GRV vaccine is safe, effectively absorbed, efficacious in inducing a rapid immune response, and effective in controlling GRV infection. Our results should be useful for the application of vaccines for controlling GRV in different goose flocks.


Dissociated cells from different layers of adult human aortic wall.
Cells isolated from a fixed adult human aorta by alcoholic-alkaline dissociation retain their intrinsic shape. They are represented by four major morphological types: stellate, elongated, elongated with side processes, and irregularly shaped cells. All the four types of cells were found in the elastic-hyperplastic intimal sublayer ; elongated and irregularly shaped cells were mainly observed in the musculoelastic sublayer and in the media. Cell density in the atherosclerotic lesion is higher than normal, the number of stellate cells being increased more substantially compared to other cell types. The origin of stellate cells and other morphological cell types, and reasons for their disproportionate accumulation in the atherosclerotic intima are discussed.


Targeting of U2AF65 to sites of active splicing in the nucleus.
U2AF65 is an essential splicing factor that promotes binding of U2 small nuclear (sn)RNP at the pre-mRNA branchpoint. Here we describe a novel monoclonal antibody that reacts specifically with U2AF65. Using this antibody, we show that U2AF65 is diffusely distributed in the nucleoplasm with additional concentration in nuclear speckles, which represent subnuclear compartments enriched in splicing snRNPs and other splicing factors. Furthermore, transient expression assays using epitope-tagged deletion mutants of U2AF65 indicate that targeting of the protein to nuclear speckles is not affected by removing either the RNA binding domain, the RS domain, or the region required for interaction with U2AF35. The association of U2AF65 with speckles persists during mitosis, when transcription and splicing are downregulated. Moreover, U2AF65 is localized to nuclear speckles in early G1 cells that were treated with transcription inhibitors during mitosis, suggesting that the localization of U2AF65 in speckles is independent of the presence of pre-mRNA in the nucleus, which is consistent with the idea that speckles represent storage sites for inactive splicing factors. After adenovirus infection, U2AF65 redistributes from the speckles and is prefferentially detected at sites of viral transcription. By combining adenoviral infection with transient expression of deletion mutants, we show a specific requirement of the RS domain for recruitment of U2AF65 to sites of active splicing in the nucleus. This suggests that interactions involving the RS region of U2AF65 may play an important role in targeting this protein to spliceosomes in vivo.


Terrestrial envenomations in pediatric patients: identification and management in the emergency department.
The majority of bites and stings from terrestrial animals are not dangerous. However, due to their smaller size, children may be more susceptible to the effects of venom, and they may experience more-severe envenomation effects than adults. This issue reviews the basic epidemiology and underlying pathophysiology of the bites and stings of spiders, bees and wasps, fire ants, scorpions, snakes, and lizards. Clinical presentations are reviewed, and evidence-based recommendations are provided for management of the envenomated patient. While the pathophysiology and much of the presentation and treatment are similar for both children and adults, there can be subtle differences, which will be highlighted in this review.


Current and novel biomarkers in anti-neutrophil cytoplasm-associated vasculitis.
Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is characterized by a variable disease course, with up to 50% of patients having one relapse within 5 years and many progressing to end-stage organ damage despite modern treatment strategies. Moreover, complications arising from treatment dominate the causes of mortality and morbidity both early and late during disease, especially in the elderly and those with severe renal involvement, and there is additional uncertainty as to how long treatment should be continued. There is, therefore, an urgent clinical need to identify robust biomarkers to better predict treatment responses, risk of disease relapse and eventual complete clinical and immunological quiescence. To date, no such biomarkers exist, but better understanding of disease pathogenesis and the underlying immune dysfunction has provided some potential candidates linked to the discovery of new antibodies, different leukocyte activation states, the role of the alternative complement pathway and markers of vascular activation. With all promising new biomarkers, there is the need to rapidly replicate and validate early findings using large biobanks of samples that could be brought together by leaders in the field.


Respiratory response to partial paralysis in anesthetized dogs.
The ability to maintain alveolar ventilation is compromised by respiratory muscle weakness. To examine the independent role of reflexly mediated neural mechanisms to decreases in the strength of contraction of respiratory muscles, we studied the effects of partial paralysis on the level and pattern of phrenic motor activity in 22 anesthetized spontaneously breathing dogs. Graded weakness induced with succinylcholine decreased tidal volume and prolonged both inspiratory and expiratory time causing hypoventilation and hypercapnia. Phrenic peak activity as well as the rate of rise of the integrated phrenic neurogram increased. However, when studied under isocapnic conditions, increases in the severity of paralysis, as assessed from the ratio of peak diaphragm electromyogram to peak phrenic activity, produced progressive increases in inspiratory time and phrenic peak activity but did not affect its rate of rise. After vagotomy, partial paralysis induced in 11 dogs with succinylcholine also prolonged the inspiratory burst of phrenic activity, indicating that vagal reflexes were not solely responsible for the alterations in respiratory timing. Muscle paresis was also induced with gallamine or dantrolene, causing similar responses of phrenic activity and respiratory timing. Thus, at constant levels of arterial CO2 in anesthetized dogs, respiratory muscle partial paralysis results in a decrease in breathing rate without changing the rate of rise of respiratory motor activity. This is not dependent solely on vagally mediated reflexes and occurs regardless of the pharmacological agent used. These observations in the anesthetized state are qualitatively different from the response to respiratory muscle paralysis or weakness observed in awake subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


Adhesion in hydrogel contacts.
A generalized thermomechanical model for adhesion was developed to elucidate the mechanisms of dissipation within the viscoelastic bulk of a hyperelastic hydrogel. Results show that in addition to the expected energy release rate of interface formation, as well as the viscous flow dissipation, the bulk composition exhibits dissipation due to phase inhomogeneity morphological changes. The mixing thermodynamics of the matrix and solvent determines the dynamics of the phase inhomogeneities, which can enhance or disrupt adhesion. The model also accounts for the time-dependent behaviour. A parameter is proposed to discern the dominant dissipation mechanism in hydrogel contact detachment.


Production and Purification of High-Titer Newcastle Disease Virus for Use in Preclinical Mouse Models of Cancer.
Newcastle disease virus (NDV) is a single-stranded, negative-sense RNA virus in the Paramyxoviridae family. Although primarily an avian pathogen, NDV is a potent oncolytic virus that has been shown to be safe and effective in a variety of preclinical cancer models and human clinical trials. To produce virus for oncolytic trials, NDV is commonly amplified in embryonated chicken eggs and purified from the allantoic fluid. Conventional methods for purifying virus from allantoic fluid often result in relatively low-titer preparations containing high levels of impurities, including immunogenic chicken host cell proteins from allantoic fluid. However, large quantities of virus need to be delivered intravenously to administer oncolytic NDV systemically to mice. This route of administration requires virus preparations that are both highly concentrated (to enable delivery of small volumes) and highly pure (to limit toxic effects from contaminants). Given the accumulation of promising preclinical and clinical data demonstrating the efficacy of NDV as an oncolytic agent, strategies for increasing the titer and purity of NDV preparations are sorely needed to allow for effective intravenous administration in mice. Here, we describe an optimized protocol for the rescue, production, and purification of high-titer in vivo-grade NDV for preclinical studies in mouse models.


[Experience with the use of posterior pituitary hormones in memory disorders of different etiology].
Results of using vasopressin and pituitrin in 20 patients with memory disturbances of various genesis (due to circulatory disturbances in the vertebrobasilar system, cerebral atherosclerosis, neurasthenia, brain concussion, epilepsy) are reviewed. The therapeutic efficacy of the hormones was evaluated with the use of a complex of psychophysiological methods. Objective changes in the patients' neurological status and subjective state were taken into account. A high therapeutic efficacy of the hormones in the treatment of amnestic syndromes is demonstrated.


Cardioprotective effect of nicorandil against myocardial injury following cardiac arrest in swine.
Nicorandil, a vasodilatory drug used to treat angina, was reported to protect against myocardial ischemia-reperfusion injury in various animal models. However, its cardioprotective action following cardiac arrest is unknown. We examined the cardioprotective effects of nicorandil in a porcine model of cardiac arrest and resuscitation. Ventricular fibrillation was induced electrically for 4min in anesthetized domestic swine, followed by cardiopulmonary resuscitation. Sixteen successfully resuscitated animals were randomized to saline control (n=8) or nicorandil (n=8) groups. Nicorandil (150μg/kg) was administered by central intravenous injection at onset of restoration of spontaneous circulation (ROSC), followed by 3μg/kg/min infusion until reperfusion end. Sham-operated animals received surgery only (n=4). Hemodynamic parameters were monitored continuously. Blood samples were taken at baseline, 5, 30, 180, and 360min after ROSC. Left ventricular ejection fraction was assessed by echocardiography at baseline and 6h after ROSC. The animals were euthanized 6h after ROSC, and the cardiac tissue was removed for analysis. 6 h after ROSC, nicorandil had significantly improved all hemodynamic variables (all P<0.05) except the maximum rate of left ventricular pressure decline and heart rate (P>0.05) compared with the control group. Control animals showed elevated cardiac troponin I and lactate levels compared with sham animals, which were significantly decreased following nicorandil treatment (P<0.05). In the saline control group, the adenosine triphosphate (ATP) content was largely reduced but subsequently rescued by nicorandil (P<0.05). Histopathologic injury was reduced with nicorandil treatment. Nicorandil reduced cardiomyocyte apoptosis as evidenced by reduced terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, decreased Bax and caspase-3 expression, and increased Bcl-2 expression in the myocardium (all P<0.05). Nicorandil exhibited cardioprotective effects on myocardial injury following cardiac arrest via improvement in post-resuscitation myocardial dysfunction and energy metabolism, reduction in myocardial histopathologic injury, and antiapoptotic effects.


Antigen-presenting properties of human vascular endothelial cells.
Human endothelial cells were obtained by collagenase digestion of the umbilical vein wall, explanted into tissue culture, and grown as monolayers of cells. Endothelial cells extracted from these monolayers were specifically lysed by anti-HLA-DR alloantisera. Moreover, the stimulating capacity of these endothelial cells toward allogeneic peripheral blood mononuclear lymphocytes was specifically and significantly inhibited by the presence of relevant anti-HLA-DR antisera. Endothelial cells that expressed HLA-DR determinants were also capable of substituting for macrophages in the lymphoproliferative response of purified T cells to soluble protein antigens. Moreover, in concordance with the results previously reported in which macrophages were employed, the endothelial cell donor should share HLA-DR determinants with the T cell donor for an optimal response to occur.


Health care access disparities among children entering kindergarten in Nevada.
The objective of this study was to advance our understanding and appreciation of the health status of young children in the state of Nevada in addition to their discrepancies in accessing health care. This study used the 2008-2009 Nevada Kindergarten Health Survey data of 11,073 children to assess both independent and combined effects of annual household income, race/ethnicity, primary language spoken in the family, rural/urban residence, and existing medical condition on access to health care. Annual household income was a significant predictor of access to health care, with middle and high income respondents having regular access to care compared to low income counterparts. Further, English proficiency was associated with access to health care, with English-speaking Hispanics over 2.5 times more likely to have regular access to care than Spanish-speaking Hispanics. Rural residents had decreased odds of access to preventive care and having a primary care provider, but unexpectedly, had increased odds of having access to dental care compared to urban residents. Finally, parents of children with no medical conditions were more likely to have access to care than those with a medical condition. The consequences for not addressing health care access issues include deteriorating health and well-being for vulnerable socio-demographic groups in the state. Altogether these findings suggest that programs and policies within the state must be sensitive to the specific needs of at risk groups, including minorities, those with low income, and regionally and linguistically isolated residents.


Effects of wax coatings and postharvest storage on sensory quality and aroma volatile composition of 'Mor' mandarins.
Mandarins suffer from accumulation of off-flavours after harvest. In this study the sensory quality and aroma profile composition of homogenised segments of untreated (control) and wax-coated 'Mor' mandarins after 7 days at 20 degrees C or 3 or 6 weeks of cold storage at 5 degrees C were examined. Fruit taste score decreased during storage and following wax coating, and this was attributed to decreases in sourness and mandarin flavour and accumulation of off-flavours. Aroma profiling identified 31 volatiles that decreased by at least 50% during storage and after waxing and thus may be involved in the observed flavour loss. In contrast, 13 volatiles, mostly belonging to ethanol fermentation and fatty acid and amino acid catabolism pathways, significantly increased at least twofold and probably contributed to off-flavour enhancement. The results showed that after harvest there was a progressive decrease in sensory quality of 'Mor' mandarins. It is proposed that observed decreases in contents of sesqui- and monoterpenes and short-chain oxygenated fatty acids may contribute to the decrease in mandarin flavour, whereas increases in the contents of ethanol fermentation metabolites and derivates of fatty acid and amino acid catabolism are most likely involved in causing the enhanced sensation of off-flavours.


Assessment of nutrition education among pediatric gastroenterologists: a survey of NASPGHAN members.
Pediatric gastroenterology is the only pediatric subspecialty with nutrition as part of its official curriculum and objective; however, pediatric gastroenterology fellows believe that their baseline knowledge in nutrition is suboptimal. The purpose of the present study was to assess the perceived effectiveness of nutrition training among pediatric gastroenterologists, identify areas of need for additional education, and determine the perceived role of the gastroenterologist in obesity management. A survey was sent to members and fellows of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition to assess general nutrition education as well as obesity management and educational needs. A total of 272 responses were received, for an overall response rate of 15.2% (272/1784). Most responders reported having average or above-average knowledge base in all nutritional topics. There was strong interest in additional resources and a continuing medical education (CME) module on several nutrition topics including nutritional requirements in specific gastrointestinal (GI) disease, failure to thrive/growth failure, and parenteral nutrition support, with the format of CME dependent on the topic. There was also a strong interest in additional CME on the management of pediatric obesity (67%), as most responders believed that the management of obesity in children requires subspecialty care. The perceived role of the pediatric gastroenterologist was, however, one of support to treat the GI and hepatic comorbidities of obesity rather than serve as the main provider of comprehensive obesity care. Pediatric gastroenterologists identified gaps in their nutrition knowledge base that may be attributed to the present nutrition education training during fellowship. Multiple topics were identified for additional nutrition education, including obesity management. The nutrition management challenges of today necessitate improved baseline nutrition knowledge and this focus on nutrition should begin at the fellowship level.


Notch receptor/ligand diversity: contribution to colorectal cancer stem cell heterogeneity.
Cancer cell heterogeneity is a key contributor to therapeutic failure and post-treatment recurrence. Targeting cell subpopulations responsible for chemoresistance and recurrence seems to be an attractive approach to improve treatment outcome in cancer patients. However, this remains challenging due to the complexity and incomplete characterization of tumor cell subpopulations. The heterogeneity of cells exhibiting stemness-related features, such as self-renewal and chemoresistance, fuels this complexity. Notch signaling is a known regulator of cancer stem cell (CSC) features in colorectal cancer (CRC), though the effects of its heterogenous signaling on CRC cell stemness are only just emerging. In this review, we discuss how Notch ligand-receptor specificity contributes to regulating stemness, self-renewal, chemoresistance and cancer stem cells heterogeneity in CRC.


Guidance on guidelines: Understanding the evidence on the uptake of health care guidelines.
Regardless of health issue, health sector, patient condition, or treatment modality, the chances are that provision is supported by "a guideline" making professionally endorsed recommendations on best practice. Against this background, research has proliferated seeking to evaluate how effectively such guidance is followed. These investigations paint a gloomy picture with many a guideline prompting lip service, inattention, and even opposition. This predicament has prompted a further literature on how to improve the uptake of guidelines, and this paper considers how to draw together lessons from these inquiries. This huge body of material presents a considerable challenge for research synthesis, and this paper produces a critical, methodological comparison of 2 types of review attempting to meet that task. Firstly, it provides an overview of the current orthodoxy, namely, "thematic reviews," which aggregate and enumerate the "barriers and facilitators" to guideline implementation. It then outlines a "realist synthesis," focussing on testing the "programme theories" that practitioners have devised to improve guideline uptake. Thematic reviews aim to provide a definitive, comprehensive catalogue of the facilitators and barriers to guideline implementation. As such, they present a restatement of the underlying problems rather than an improvement strategy. The realist approach assumes that the incorporation of any guideline into current practice will produce unintended system strains as different stakeholders wrestle over responsibilities. These distortions will prompt supplementary revisions to guidelines, which in turn beget further strains. Realist reviews follow this dynamic understanding of organisational change. Health care decision makers operate in systems that are awash with guidelines. But guidelines only have paper authority. Managers do not need a checklist of their pros and cons, because the fate of guidelines depends on their reception rather than their production. They do need decision support on how to engineer and reengineer guidelines so they dovetail with evolving systems of health care delivery.


Genotypic Detection of qnrA and qnrC Genes in Citrobacter koseri Isolated from Patients with Urinary Tract Infection.
The urinary tract infection (UTI) is a prevalent infection that affects people of all ages. Bacterial agents are the most common causes of UTIs. Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and other staphylococcal species, Citrobacter freundii and Citrobacter koseri (C. koseri) account for a smaller number of infections. These pathogens are transported into the urinary tract from the colonic biotope into dysbacteriosis. Urine samples were randomly collected from 249 outpatients who were suspected of having UTIs. After genital cleaning, 10 mL of urine specimens were collected in a sterilized bowel. Then, the specimens were centrifuged at 2,000 rpm for 5 min and the residue was aerobically incubated with the broth infusion of brain flasks at 37°C for 24 h and then applied with a sterile ring onto blood agar plates and MacConkey agar (OxoidTM). Out of 249 urine samples, the results proved that there were 176 (70.7%) and 51(20.5%) gram-negative and gram-positive bacteria isolates, respectively. However, the results demonstrated that there were 22 (8.8%) urine samples with no growth. In addition, the results showed that eight various antimicrobials are used to treat C. koseri. In the current study, C. koseri was treated with eight different antimicrobial agents. The antimicrobial resistance rate for 7 isolates against Cefotaxime, Ceftriaxone, Ciprofloxacin, and Levofloxacin was high for 6 (85.71%) isolates. The results indicated that 6 and 5 isolates had 85.71% and 71.42% antimicrobial resistance against Ceftazidime and Levofloxacin, respectively. Whereas Gentamicin showed a moderate rate of resistance (4 isolates, 57.14%), and Amikacin resistance was found in 5 isolates, accounting for 28.57%. The bacterial isolates had a high susceptibility rate to Imipenem. The qnrA gene was found in 6 (85.71%) isolates. However, the recorded data demonstrated that there is no isolate carrying the qnrC gene. Among all pathogenic bacteria, C. koseri was the lowest causative agent of UTI in this study and was highly resistant to most antimicrobials except Imipenem, which was a good antibiotic with 100% sensitivity.


Clinical features and management of atypical hemolytic uremic syndrome patient with DGKE gene variants: a case report.
Atypical hemolytic uremic syndrome (aHUS) with diacylglycerol kinase epsilon (DGKE) gene variant is a rare variant of thrombotic microangiopathy (TMA). The information on the clinical features, management and long-term outcomes of DGKE-aHUS patients have not yet been fully elucidated. The aim of this study was to report a novel variant of the DGKE gene in a Chinese population with aHUS. The present work reports a 7-month-old boy with aHUS, possibly triggered by gastrointestinal infection, without complement activation, with little response to plasma therapy and nephroprotective measures. The patient died during the 8th week of his hospital stay. The causes of death were intracranial hemorrhage and multiorgan dysfunction. Comprehensive WES of peripheral blood-derived DNA revealed two heterozygous variations in the DGKE exon region: NM_003647.2, c.610dup, p.Thr204Asnfs*4 and deletion of exons 4-6. This case suggest that atypical HUS with DGKE gene variant has a poor prognosis with a high mortality rate, which typically manifests in the first year of life and presents as a systemic disease with early-onset HUS with rapidly worsening renal function and chronic proteinuria. There is no specific treatment for DGKE-aHUS. There have an uncertain benefit of plasma therapy for DGKE-aHUS patients. The literature demonstrated that anti-complement therapy showed benefits for DGKE-aHUS with complement activation and autoantibodies during the overt TMA presentation but did not prevent TMA relapses. Early diagnosis and treatment may prevent complications and improve prognosis.


Ryanodine receptor-transmitter release site coupling increases quantal size in a synapse-specific manner.
The mechanisms by which presynaptic neurones differentially regulate synaptic transmission with multiple postsynaptic targets in the brain are not fully understood. Using intracellular sharp electrode and whole-cell voltage-clamp recordings of soma-soma synapses between identified Lymnaea neurones, we provide direct evidence that quantal size is regulated presynaptically through the coupling of multiple release sites. This coupling effectively multiplies quantal size, thereby providing significant influence over parameters of synaptic transmission that are influenced by quantal size, such as the variance in transmitter release at stationary release probabilities. Variation in the degree of coupling is dependent on the identity of the postsynaptic cell, even though the variation in quantal size is of presynaptic origin. We have therefore demonstrated the presence of a novel mechanism by which presynaptic neurones may differentially regulate quantal size at select synaptic connections, in turn providing them with a means of regulating synaptic transmission with multiple postsynaptic cells.


Limited Impact of Human Cytomegalovirus Infection in African Infants on Vaccine-Specific Responses Following Diphtheria-Tetanus-Pertussis and Measles Vaccination.
Human cytomegalovirus (HCMV) infection has a profound effect on the human immune system, causing massive clonal expansion of CD8, and to a lesser extend CD4 T cells. The few human trials that have explored the effect of HCMV infection on responses to vaccination are conflicting, with some studies suggesting no effect whilst others suggest decreased or increased immune responses. Recent studies indicate substantial differences in overall immune system reactivity to vaccines based on age and sex, particularly cellular immunity. 225 nine-month old Gambian infants were immunized with diphtheria-tetanus-whole cell pertussis and/or measles vaccines. HCMV infection status was determined by the presence of CMV DNA by PCR of urine samples prior to vaccination. The effect of HCMV infection on either protective antibody immunity or vaccine-specific and overall cellular immune responses 4 weeks post-vaccination was determined, further stratified by sex. Tetanus toxoid-specific antibody responses were significantly lower in HCMV+ infants compared to their HCMV- counterparts, while pertussis, diphtheria and measles antibody responses were generally comparable between the groups. Responses to general T cell stimulation with anti-CD3/anti-CD28 as well as antigen-specific cytokine responses to purified protein derivative (PPD) were broadly suppressed in infants infected with HCMV but, perhaps surprisingly, there was only a minimal impact on antigen-specific cellular responses to vaccine antigens. There was evidence for subtle sex differences in the effects of HCMV infection, in keeping with the emerging evidence suggesting sex differences in homeostatic immunity and in responses to vaccines. This study reassuringly suggests that the high rates of HCMV infection in low income settings have little clinically significant impact on antibody and cellular responses to early life vaccines, while confirming the importance of sex stratification in such studies.


PIC profiles for learning-disabled and behavior-disordered children.
Compared the performance of learning-disabled and behavior-disordered children (N = 60) on the recently published Personality Inventory of Children (PIC) to investigate the discriminant validity of the instrument. The data were analyzed by profile analysis and stepwise discriminant analysis. Results showed that learning-disabled and behavior-disordered children could be differentiated clearly on subtests that comprise the Cognitive Development and Conduct Disorder factors. However, less differentiation was found on the Internalization factor. Further examination indicated a possible diagnosis X scale "interaction" within the Internalization factor. Those learning-disabled children who also experienced "internal" difficulties tended to score high on the Somatic Concern Scale, while behavior-disordered children typically scored high on the other Internalization scales (i.e., Anxiety, Withdrawal, etc.). A total of seven of the PIC clinical and validity scales were selected in the discriminant function that separated the two groups.


Occupational exposure to trichloroethylene and risk of non-Hodgkin lymphoma and its major subtypes: a pooled InterLymph [correction of IinterLlymph] analysis.
We evaluated the association between occupational exposure to trichloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL) in a pooled analysis of four international case-control studies. Overall, the pooled study population included 3788 NHL cases and 4279 controls. Risk of NHL and its major subtypes associated with TCE exposure was calculated with unconditional logistic regression and polytomous regression analysis, adjusting by age, gender and study. Risk of follicular lymphoma (FL), but not NHL overall or other subtypes, increased by probability (p=0.02) and intensity level (p=0.04), and with the combined analysis of four exposure metrics assumed as independent (p=0.004). After restricting the analysis to the most likely exposed study subjects, risk of NHL overall, FL and chronic lymphocytic leukaemia (CLL) were elevated and increased by duration of exposure (p=0.009, p=0.04 and p=0.01, respectively) and with the combined analysis of duration, frequency and intensity of exposure (p=0.004, p=0.015 and p=0.005, respectively). Although based on small numbers of exposed, risk of all the major NHL subtypes, namely diffuse large B-cell lymphoma, FL and CLL, showed increases in risk ranging 2-3.2-fold in the highest category of exposure intensity. No significant heterogeneity in risk was detected by major NHL subtypes or by study. Our pooled analysis apparently supports the hypothesis of an increase in risk of specific NHL subtypes associated with occupational exposure to TCE.


Hierarchical organization of long-range circuits in the olfactory cortices.
How sensory information is processed within olfactory cortices is unclear. Here, we examined long-range circuit wiring between different olfactory cortical regions of acute mouse brain slices using a channelrhodopsin-2 (ChR2)-based neuronal targeting approach. Our results provide detailed information regarding the synaptic properties of the reciprocal long-range monosynaptic glutamatergic projections (LRMGP) between and within anterior piriform cortex (aPC), posterior piriform cortex (pPC), and lateral entorhinal cortex (LEC), thereby creating a long-range inter- and intracortical circuit diagrams at the level of synapses and single cortical neurons. Our results reveal the following information regarding hierarchical intra- and intercortical organizations: (i) there is massive bottom-up (i.e., rostral-caudal) excitation within the LRMGP accompanied with strong feedforward (FF) inhibition; (ii) there are convergent FF connections onto LEC from both aPC and pPC; (iii) feedback (FB) intercortical connections are weak with a significant fraction of presumptive silent synapses; and (iv) intra and intercortical long-range connections lack layer specificity and their innervation of interneurons are stronger than neighboring pyramidal neurons. The elucidation of the distinct hierarchical organization of long-range olfactory cortical circuits paves the way for further understanding of higher order cortical processing within the olfactory system.


Computed tomography of bladder leiomyoma.
A case of bladder leiomyoma is reported with computed tomographic (CT) features suggesting a malignant epithelial tumor. Cystoscopy demonstrated intact mucosa stretched over a submucosal tumor and suggested the diagnosis of leiomyoma. Direct coronal CT confirmed the origin of the tumor within the bladder rather than within the uterus.


[Dilated cardiomyopathy: indication and role of non-invasive instrumental evaluation].
Typical morphological and functional abnormalities of dilated cardiomyopathy can be well evaluated non-invasively by the echocardiographic and echo-Doppler study. However it is important to remember that left ventricular dilation and depressed systolic function can be found also in other diseases that may mimic idiopathic dilated cardiomyopathy (coronary heart disease, myocarditis, biventricular dysplasia, advanced hypertrophic cardiomyopathy, hypertensive or valvular heart diseases). Unusual echocardiographic findings for dilated cardiomyopathy, i.e. a mildly dilated and/or hypertrophic left ventricle, segmental rather than diffuse wall motion abnormalities, predominant right ventricular dilation and dysfunction or severe valvular abnormalities should increase the clinical suspicion of a different disease. Transesophageal and dobutamine stress echocardiography can be employed in selected patients. However, for definitive diagnosis invasive hemodynamic study with coronary angiography and sometimes endomyocardial biopsy is often required. The diagnostic role of other non-invasive studies, such as magnetic resonance, computed tomography and nuclear techniques, is not well known, considering the cost and the limited availability of these clinical tools.


Littoral cell angioma: A case report.
Primary splenic lesions are rare entities among which littoral cell angioma (LCA) is a recently described, uncommon vascular lesion that is unique to the spleen. It has heretofore been described primarily in pathologic series and has been found mostly to behave as a benign entity. A few reports of malignant variants have been reported. We present a case report of a solitary LCA discovered after splenectomy for an incidentally discovered splenic lesion, along with a literature review.


Evidence for an apartheid-like social structure in early Anglo-Saxon England.
The role of migration in the Anglo-Saxon transition in England remains controversial. Archaeological and historical evidence is inconclusive, but current estimates of the contribution of migrants to the English population range from less than 10000 to as many as 200000. In contrast, recent studies based on Y-chromosome variation posit a considerably higher contribution to the modern English gene pool (50-100%). Historical evidence suggests that following the Anglo-Saxon transition, people of indigenous ethnicity were at an economic and legal disadvantage compared to those having Anglo-Saxon ethnicity. It is likely that such a disadvantage would lead to differential reproductive success. We examine the effect of differential reproductive success, coupled with limited intermarriage between distinct ethnic groups, on the spread of genetic variants. Computer simulations indicate that a social structure limiting intermarriage between indigenous Britons and an initially small Anglo-Saxon immigrant population provide a plausible explanation of the high degree of Continental male-line ancestry in England.


Touch Inventory for Elementary-School-Aged Children.
The syndrome of tactile defensiveness, first described by Ayres in 1964, has undergone continued study as well as related theory development. No standardized assessment for tactile defensiveness, however, currently exists. This paper presents a 26-item screening scale, the Touch Inventory for Elementary-School-Aged Children (TIE), as well as its psychometric characteristics. Normative data and precautions for proper use of the TIE are also given.


Gender-based violence and HIV: relevance for HIV prevention in hyperendemic countries of southern Africa.
Gender-based violence (GBV) is common in southern Africa. Here we use GBV to include sexual and non-sexual physical violence, emotional abuse, and forms of child sexual abuse. A sizeable literature now links GBV and HIV infection.Sexual violence can lead to HIV infection directly, as trauma increases the risk of transmission. More importantly, GBV increases HIV risk indirectly. Victims of childhood sexual abuse are more likely to be HIV positive, and to have high risk behaviours.GBV perpetrators are at risk of HIV infection, as their victims have often been victimised before and have a high risk of infection. Including perpetrators and victims, perhaps one third of the southern African population is involved in the GBV-HIV dynamic.A randomised controlled trial of income enhancement and gender training reduced GBV and HIV risk behaviours, and a trial of a learning programme reported a non-significant reduction in HIV incidence and reduction of male risk behaviours (primary prevention). Interventions among survivors of GBV can reduce their HIV risk (secondary prevention). Various strategies can reduce spread of HIV from infected GBV survivors (tertiary prevention). Dealing with GBV could have an important effect on the HIV epidemic.A policy shift is necessary. HIV prevention policy should recognise the direct and indirect implications of GBV for HIV prevention, the importance of perpetrator dynamics, and that reduction of GBV should be part of HIV prevention programmes. Effective interventions are likely to include a structural component, and a GBV awareness component.


Verifying Identities of Plant-Based Multivitamins Using Phytochemical Fingerprinting in Combination with Multiple Bioassays.
Sales of multivitamins have been growing rapidly and the concept of natural multivitamin, plant-based multivitamin, or both has been introduced in the market, leading consumers to anticipate additional health benefits from phytochemicals that accompany the vitamins. However, the lack of labeling requirements might lead to fraudulent claims. Therefore, the objective of this study was to develop a strategy to verify identity of plant-based multivitamins. Phytochemical fingerprinting was used to discriminate identities. In addition, multiple bioassays were performed to determine total antioxidant capacity. A statistical computation model was then used to measure contributions of phytochemicals and vitamins to antioxidant activities. Fifteen multivitamins were purchased from the local markets in Seoul, Korea and classified into three groups according to the number of plant ingredients. Pearson correlation analysis among antioxidant capacities, amount phenols, and number of plant ingredients revealed that ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryhydrazyl (DPPH) assay results had the highest correlation with total phenol content. This suggests that FRAP and DPPH assays are useful for characterizing plant-derived multivitamins. Furthermore, net effect linear regression analysis confirmed that the contribution of phytochemicals to total antioxidant capacities was always relatively higher than that of vitamins. Taken together, the results suggest that phytochemical fingerprinting in combination with multiple bioassays could be used as a strategy to determine whether plant-derived multivitamins could provide additional health benefits beyond their nutritional value.


Long Noncoding RNA OR7E156P/miR-143/HIF1A Axis Modulates the Malignant Behaviors of Glioma Cell and Tumor Growth in Mice.
Gliomas are characterized by high incidence, recurrence and mortality all of which are significant challenges to efficacious clinical treatment. The hypoxic microenvironment in the inner core and intermediate layer of the tumor mass of gliomas is a critical contributor to glioma pathogenesis. In this study, we identified an upregulated lncRNA, OR7E156P, in glioma was identified. The silencing of OR7E156P inhibited cell invasion and DNA synthesis in vitro and tumor growth in vivo. OR7E156P was intricately linked to the HIF1A pathway. Hypoxia could induce OR7E156P expression, whereas OR7E156P silencing decreased HIF1A protein levels under hypoxic conditions. Hypoxia promoted glioma cell invasion and DNA synthesis, and HUVEC tube formation, whereas OR7E156P silencing partially reversed the cellular effects of hypoxia. HIF1A overexpression promoted, whereas OR7E156P silencing inhibited tumor growth; the inhibitory effects of OR7E156P silencing on tumor growth were partially reversed by HIF1A overexpression. miR-143 directly targeted OR7E156P and HIF1A, respectively. miR-143 inhibition increased HIF1A protein levels, promoted glioma cell invasion and DNA synthesis. Moreover, they enhanced HUVEC tube formation, whereas OR7E156P silencing partially reversed the cellular effects of miR-143 inhibition. HIF1A targeted the promoter region of miR-143 and inhibited miR-143 expression. Altogether a regulatory axis consisting of OR7E156P, miR-143, and HIF1A, was identified which is deregulated in glioma, and the process of the OR7E156P/miR-143/HIF1A axis modulating glioma cell invasion through ZEB1 and HUVEC tube formation through VEGF was demonstrated.


Regulatory networks and complex interactions between the insulin and angiotensin II signalling systems: models and implications for hypertension and diabetes.
The cross-talk between insulin and angiotensin II signalling pathways plays a significant role in the co-occurrence of diabetes and hypertension. We developed a mathematical model of the system of interactions among the biomolecules that are involved in the cross-talk between the insulin and angiotensin II signalling pathways. We have identified several feedback structures that regulate the dynamic behavior of the individual signalling pathways and their interactions. Different scenarios are simulated and dominant steady-state, dynamic and stability characteristics are revealed. The proposed mechanistic model describes how angiotensin II inhibits the actions of insulin and impairs the insulin-mediated vasodilation. The model also predicts that poor glycaemic control induced by diabetes contributes to hypertension by activating the renin angiotensin aystem.


Immune response versus susceptibility to Marek's disease.
It was hypothesized that the generation of activated T cells through an efficient and rapid immune response during the early pathogenesis of Marek's disease virus (MDV) infection provides a large pool of target cells for transformation. Therefore, the correlation between genetic susceptibility to Marek's disease (MD) and in vitro mitogenic responses of lymphocytes as a measure of cell-mediated immune competence and efficiency was tested. In one series of trials, spleen cells from strains of chickens with differing levels of susceptibility to MD tumors were stimulated with graded doses of Concanavalin A (Con A) or phytohemagglutin (PHA). In a second series of trials, peripheral blood lymphocytes from individual chickens within genetic strains were tested at the same time chickens were challenged with MDV to determine susceptibility. Responsiveness was determined using one-way mixed lymphocyte reaction (MLR) tests as well as mitogen stimulation. Data from the tests comparing chicken strains supported the hypothesis in some but not all cases. The S13 chickens, which are more susceptible than P2a chickens to MD, were significantly more responsive, and highly resistant N2a chickens were significantly less responsive to Con A. In contrast, five other resistant strains were either more responsive (UCD-058, OS13) or equally responsive (UCD-140, OS5, C) to Con A when compared with P2a chickens. The PHA responses were even less predictive of MD susceptibility. No general correlation was observed between responsiveness to either mitogen or MLR tests and subsequent tumor development in trials comparing individuals within strains.


Body composition analysis and estimation of physical fitness by scoring grades in Saudi adults.
To determine the prevalence of different categories of body composition in healthy Saudi adults and its relationship with fitness scoring. The cross-sectional study was conducted on 428 healthy adult Saudi subjects over 18 years of age conducted at the department of Physiology, College of Medicine, King Khalid University Hospital, King Saud University, Saudia Arabia from April 2010 to September 2011. All participants underwent body composition analysis assessed by bioelectrical impendence analysis. Measurements included body weight, body mass index, protein mass, fat mass, percent body fat, and fitness scoring based on the target values. SPSS 10 was used for statistical analysis. The mean age of the participants was 36.90 +/- 15.22 years, ranging from 18 to 72 years. There were 318 (74.3%) males and 110 (25.7%) females. The mean body mass index and fitness scores were 27.22 +/- 5.65 and 69.3 +/- 8.48 respectively. The per cent prevalence of underweight, normal weight, overweight, obesity class I, obesity class II and obesity class III was 2.91 (n = 13), 33.81 (n = 139), 35.27 (n = 145), 19.46 (n = 80), 6.32 (n = 26) and 2.18 (n = 9) respectively. Of the total, 57 (13.4%) individuals had poor fitness, while 123 (28.7%) had fair fitness scores. Good fitness score was seen in 218 (50.9%). Only 33 (7.8%) subjects had normal body fats and 46 (10.7%) showed lesser body fats than required. While the percentage of subjects with extra body fats ranging from < 2 kg, 2-4.9, 5.0-9.9, 10.0-14.9,15-19.9 and > 20 kg was 12.1 (n = 52), 19.4 (n = 83), 15.6 (n = 67), 15.2 (n = 65), 9.0 (n = 38) and 10.3 (n = 44) respectively. Significant gender differences were observed in body mass index, fitness score, per cent body fat and other parametres of body composition. The prevalence of obesity, per cent body fat and poor fitness was high in the study population with significant gender differences. Public awareness programmes, including exercise and diet teaching, are required at mass scale to cope up with the growing burden of obesity.


Association of herpes simplex virus type 1 ICP8 and ICP27 proteins with cellular RNA polymerase II holoenzyme.
Herpes simplex virus 1 (HSV-1) infection causes the shutoff of host gene transcription and the induction of a transcriptional program of viral gene expression. Cellular RNA polymerase II is responsible for transcription of all the viral genes, but several viral proteins stimulate viral gene transcription. ICP4 is required for all delayed-early and late gene transcription, ICP0 stimulates transcription of viral genes, and ICP27 stimulates expression of some early genes and transcription of at least some late viral genes. The early DNA-binding protein, ICP8, also stimulates late gene transcription. We therefore investigated which HSV proteins interact with RNA polymerase II. Using immunoprecipitation and Western blotting methods, we observed the coprecipitation of ICP27 and ICP8 with RNA polymerase II holoenzyme. The association of ICP27 with RNA polymerase II was detectable as early as 3 h postinfection, while ICP8 association became evident by 5 h postinfection, and the association of both was independent of viral DNA synthesis. Infections with ICP27 gene mutant viruses revealed that ICP27 is required for the association of ICP8 with RNA polymerase II, while studies with ICP8 gene deletion mutants showed no apparent role for ICP8 in the association of ICP27 with RNA polymerase II. The association of ICP27 and ICP8 with RNA polymerase II holoenzyme appeared to be independent of nucleic acids. We hypothesize that the interaction of ICP27 with RNA polymerase II holoenzyme reflects its role in stimulating early and late gene expression and/or its role in inhibiting host transcription and that the interaction of ICP8 with RNA polymerase II holoenzyme reflects its role in stimulating late gene transcription.


Influence of imidazolium based green solvents on volume phase transition temperature of crosslinked poly(N-isopropylacrylamide-co-acrylic acid) hydrogel.
The volume phase transition temperature (VPTT) of crosslinked poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAM-co-AA) hydrogel in water in the presence of five imidazolium based ionic liquids (ILs) was studied. The VPTT of PNIPAM-co-AA hydrogel can be modulated to different extents by the addition of different amounts of ILs. The modulations in VPTT values can be attributed to the IL-induced alterations in hydrophobic, hydrophilic and hydrogen bonding interactions of PNIPAM-co-AA hydrogel with the neighboring solvent and molecular chains. The influence of ILs having a common cation, 1-butyl-3-methylimidazolium cation ([Bmim]) and different anions, such as iodide (I-), tetrafluoroborate (BF4-), chloride (Cl-), acetate (CH3COO-) and hydrogen sulfate (HSO4-), on the phase transition of PNIPAM-co-AA hydrogel was monitored by the aid of differential scanning calorimetry (DSC), dynamic light scattering (DLS) and Fourier transform infrared (FT-IR) spectroscopy. Furthermore, the interfacial properties between aqueous IL and polymer surface were scrutinized with the help of contact angle (CA) measurements. The overall specific ranking of ILs in preserving the hydration layer around the PNIPAM-co-AA hydrogel in water was [Bmim][I]>[Bmim][BF4]>[Bmim][Cl]>[Bmim][Ac]>[Bmim][HSO4]. The trend of these ILs followed the well-known Hofmeister series. Interestingly, the PNIPAM-co-AA hydrogel in water shows abnormal salting-out property in the presence of [Bmim][BF4] at higher concentration and this abnormal behavior can be explained based on the lack of sufficient binding sites on the macromolecule for higher number of [Bmim][BF4] at a higher concentration.


Evaluation of the effect of endotracheal aspiration at different head heights on oxygenation of the brain by non-invasive method in intensive care patients.
To determine the effect of endotracheal aspiration at different head heights on oxygenation brain by non-invasive method in neurosurgery intensive care patients. Head elevation of mechanical ventilator-dependent neurosurgery patients and the possible risks of endotracheal aspiration are closely related to the clinical conditions of the patients. A prospective quasi-experimental study with repetitive measurements in a single group. In the study, neurosurgery intensive care patients were adjusted to a head height of 15, 30 and 45° (n = 46, power analysis %90). Cerebral oxygenation levels were determined with a non-invasive device at each head height before and in the 1st, 5th and 30th min of endotracheal aspiration. Data were collected with Patient Information Form and cerebral oxygenation device based on NIRS technology. This study performed according to the TREND reporting guidelines for non-randomized/quasi experimental study. The highest cerebral oxygenation value was obtained at 30 min. The decrease in the cerebral oxygenation levels of the patients was highest in the 1st min after endotracheal aspiration, at a head height of 15 degrees for the right cerebral region and at a head height of 30 degrees for the left cerebral region. The increase in oxygenation of the right and left cerebral regions occurred highest at a head height of 45 degrees. The ideal head height should be 45 degrees during and after endotracheal aspiration in regard to maintaining cerebral oxygenation in neurosurgery intensive care patients. It is extremely important to monitor the cerebral oxygenation status of patients, with non-invasive measurement tools during and after endotracheal aspiration, to prevent secondary complications. This study reveals the importance of raising the head 45 degrees in the best preservation of cerebral oxygenation values in neurosurgery intensive care patients. Intensive care nurses should pay attention to maintaining this head height.


Graph MADDPG with RNN for multiagent cooperative environment.
Multiagent systems face numerous challenges due to environmental uncertainty, with scalability being a critical issue. To address this, we propose a novel multi-agent cooperative model based on a graph attention network. Our approach considers the relationship between agents and continuous action spaces, utilizing graph convolution and recurrent neural networks to define these relationships. Graph convolution is used to define the relationship between agents, while recurrent neural networks define continuous action spaces. We optimize and model the multiagent system by encoding the interaction weights among agents using the graph neural network and the weights between continuous action spaces using the recurrent neural network. We evaluate the performance of our proposed model by conducting experimental simulations using a 3D wargame engine that involves several unmanned air vehicles (UAVs) acting as attackers and radar stations acting as defenders, where both sides have the ability to detect each other. The results demonstrate that our proposed model outperforms the current state-of-the-art methods in terms of scalability, robustness, and learning efficiency.


Optical coherence tomography (OCT): ready for the diagnosis of a nephrogenic adenoma of the urinary bladder?
The feasibility of Optical Coherence Tomography (OCT) as a non-invasive technique was shown in different fields. We investigated OCT's potential to detect nephrogenic adenoma (NA) within the human bladder. Clinically non-invasive methods like ultrasonography or CT have significant limitations. We applied our experience from OCT-analyses to one case of NA. OCT in vivo examination was performed using an optical fiber which was positioned cystoscopically. Characteristic structures of NA were compared in the OCT-images and the hematoxylin and eosin histological samples. Indeed, the structure and exact position of NA could be defined in relation to surrounding layers. However, a definite classification as NA by OCT only could not be reached in this single case. The examination of more NA cases would be necessary to base well-founded conclusions on. Further development of this technology could lead to an optical substitute for biopsies: especially apt for the field of endourology.


The assessment of platelet derived growth factor concentration in post myocardial infarction and stable angina patients.
Platelet derived growth factor (PDGF) has been implicated in the pathogenesis of atherosclerosis. PDGF is released by aggregating platelets and monocytes which gather around sites of arterial injury. In the study reported here the concentration of plasma PDGF was measured in post myocardial infarction (MI) patients (n = 28), angina patients (n = 25), and control subjects (n = 27). Venous blood samples were taken and the concentration of PDGF determined by an enzyme linked immunosorbent assay (ELISA). Plasma PDGF concentrations were significantly higher in the post MI group compared to both the control and angina groups (P < or = 0.05). The increase in PDGF concentration may be due to increased activation of platelets or monocytes since these two cells are major sources of plasma PDGF. High concentrations of PDGF in the circulation could further accelerate the progression of the disease.


Cohort Profile: Tracing Achievements, Key processes and Efforts in professional care for Children and Adolescents REsearch; TAKECARE.
TAKECARE is a prospective cohort study designed in The Netherlands to obtain evidence on the care chain for children and adolescents with psychosocial problems, and its long-term outcomes. Little is known about the content of care as offered and on whether the care is adequate. The cohort consists of children and adolescents entering care for psychosocial problems (care sample, n = 1382) and a random sample of the general population (community sample, n = 666). Children were eligible for participation if they were aged 4-18 years (inclusive) and had estimated IQs of 70 and over. The care sample covers the fields of Preventive Child Healthcare (PCH), Child and Adolescent Social Care (CASC) and Child and Adolescent Mental Healthcare (CAMH). Children, parents or guardians and involved practitioners completed five questionnaires (baseline, and at 3, 12, 24 and 36 months thereafter). The main categories of data concern the sociodemographic characteristics of children and their parents or guardians, the characteristics of entry into care and care content, and intermediate and final treatment outcomes. Information about data access can be requested by e-mail: email@example.com.


Repeated exposure to alcoholic beer does not induce long-lasting changes in alcohol self-administration and intake in Sardinian alcohol-preferring and Sardinian non-preferring rats.
Rats avidly consume non-alcoholic beer, and addition of alcohol to non-alcoholic beer may function as a medium to induce intake of large amounts of alcohol in rats. The present study investigated whether Sardinian alcohol-preferring (sP) and Sardinian non-preferring (sNP) rats, initially exposed to non-alcoholic beer, and subsequently to non-alcoholic beer containing increasing concentrations of alcohol, would develop unusually high alcohol self-administration and drinking behaviours: (i) when alcohol was added to non-alcoholic beer, and (2) once beer was withdrawn and a plain alcohol solution was made available. In Experiment 1, rats were exposed to operant, 30-min/day self-administration sessions of non-alcoholic beer with increasing concentrations of alcohol [0, 2.5, 5, 7.5, and 10% (v/v)] for a total of 45 days. After a brief 'beer-fading' phase, the rats were exposed to self-administration sessions of a plain 10% (v/v) alcohol solution. In Experiment 2, the rats were exposed to non-alcoholic beer with increasing concentrations of alcohol [0, 2.5, 5, 7.5, and 10% (v/v)] and water under the 2-bottle choice regimen with unlimited access (24 h/day) for a total of 35 days. After a brief 'beer-fading' phase, the rats were exposed to the choice between a plain 10% (v/v) alcohol solution and water. sP and sNP rats did not differ in self-administration (Experiment 1) and intake (Experiment 2) of non-alcoholic beer. In Experiment 1, as alcohol content increased, the amount of self-administered alcohol increased progressively in sP rats (up to 1-1.2 g/kg) and remained stable in sNP rats (approximately 0.65 g/kg). When the plain 10% alcohol solution was available, the amount of self-administered alcohol in sP rats initially dropped, and tended to increase-up to approximately 0.6 g/kg-on continuing exposure. In sNP rats, their lever-pressing behaviour was rapidly extinguished after beer withdrawal. In Experiment 2, as alcohol content was increased, daily alcohol intake increased progressively in sP rats (up to 8-9 g/kg) and averaged approximately 2.4 g/kg in sNP rats. When the plain alcohol solution was available, daily alcohol intake in sP rats was initially low, reaching control values on continuing exposure; conversely, daily alcohol intake was completely suppressed in sNP rats. These results suggest that exposure to alcoholic beer resulted in unusually high intakes of alcohol in both sP and sNP rats for as long as non-alcoholic beer was added to alcohol; however, these high levels of alcohol self-administration and intake were not maintained once non-alcoholic beer was withdrawn.


Effect of potato inhibitor of proteolytic enzymes on rat pancreas morphology. Part II.
The effect of potato inhibitor of proteolytic enzymes on the ultrastructure of rat pancreas was investigated administering the inhibitor with drinking water in 100 mg doses during 20 days. On the 21st day of the experiment the pancreas was removed and sections were taken from the body of the gland for examinations in electron microscope. Ultrastructural investigations showed that the inhibitor exerted a trophic effect on the pancreas expressed as a stronger activity of the acinar cells in which increased number of zymogen granules were found. In pancreatic homogenates a reduction of the RNA/DNA ratio was demonstrated in the group of rats receiving the inhibitor, which suggests hyperplasia of the acinar pancreatic cells in relation to the control group of rats. The obtained results of ultrastructural and biochemical investigations in the pancreas of inhibitor-receiving rats are a confirmation of the results of investigations carried out under light microscope, and they explain the cause of increased exocrine activity of the pancreas.


Urothelial Dysfunction and Chronic Inflammation are Associated With Increased Bladder Sensation in Patients With Chronic Renal Insufficiency.
Chronic kidney disease (CKD) or end-stage renal disease (ESRD) patients usually have lower urinary tract symptoms, such as frequency and urgency. Additionally, they frequently suffer from urinary tract infections. This study investigated dysfunction and chronic inflammation of the bladder urothelium in ESRD/CKD patients. This study enrolled 27 patients with CKD (n=13) or ESRD (n=14) for urodynamic studies and bladder biopsies. Patients presented with detrusor underactivity (DU; n=8) or bladder oversensitivity (BO; n=19). Bladder biopsies were performed in these patients and in 20 controls. The bladder mucosa was examined for E-cadherin and zonula occludens-1 (ZO-1) expression, activated mast cell count (through tryptase staining), and urothelial apoptosis (through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling [TUNEL]). The urodynamic parameters were also compared with variables regarding urothelial dysfunction. The bladder mucosa samples of ESRD and CKD patients revealed significantly higher mast cell counts, more urothelial apoptosis, and lower levels of ZO-1 expression than the control samples. E-cadherin expression was significantly reduced in ESRD/CKD patients with DU, but not in ESRD/CKD patients with BO. Increased mast cell and apoptotic cell counts were also associated with ESRD/CKD with BO. Less expression of ZO-1 and E-cadherin was significantly associated with increased bladder sensation and a small bladder capacity. Bladder urothelial dysfunction and chronic inflammation were present to a noteworthy extent in patients with ESRD or CKD. Increased inflammation and defective barrier function were more notable in ESRD/CKD bladders with BO than in those with DU. The clinical characteristics of these patients may involve urothelial pathophysiology.


Derivation and validation of a quantitative definition of specific reading disability for adults.
One hundred and fifty-four adult relatives of children with specific reading disability, and a group of 90 adults matched for age, sex, educational level and IQ, were given a battery of intelligence, reading and spelling tests and a questionnaire on their reading history, habits and attitudes. Data obtained from the latter group were used to derive multiple regression equations for the prediction of reading and spelling scores. An index was derived for each adult, expressing actual scores relative to those predicted. A definition of severe and borderline reading disability was validated, using the scores from the questionnaire.


External radiotherapy and extrahepatic bile duct cancer.
The hospital records of patients with extrahepatic bile duct cancer who where treated surgically between 1968 and 1983 were reviewed. Of 55 patients, 16 (29%) received radiotherapy after surgery. The total dose given ranged from 40 to 60 Gy. Median follow-up time for analysis was 4.0 months and lasted until January 1988. The overall median survival was 4 months (range 0-36), that of the irradiated patients was 16 months (range 2-36), and that of the 39 patients who were not irradiated was 3 months (range 0-32). When the 13 post operative deaths were excluded the median survival was 4 months. Radiotherapy did not cause any severe complications. No firm conclusion about the role of radiotherapy can be drawn from these data because the patients were not randomly chosen to receive radiotherapy and selection was therefore biased. We conclude that most patients with extrahepatic bile duct cancer still die of locoregional disease. Effective adjuvant treatments are needed and should be evaluated in prospective randomized trials.


Evolutionary dynamics of whole-body regeneration across planarian flatworms.
Regenerative abilities vary dramatically across animals. Even amongst planarian flatworms, well-known for complete regeneration from tiny body fragments, some species have restricted regeneration abilities while others are almost entirely regeneration incompetent. Here, we assemble a diverse live collection of 40 planarian species to probe the evolution of head regeneration in the group. Combining quantification of species-specific head-regeneration abilities with a comprehensive transcriptome-based phylogeny reconstruction, we show multiple independent transitions between robust whole-body regeneration and restricted regeneration in freshwater species. RNA-mediated genetic interference inhibition of canonical Wnt signalling in RNA-mediated genetic interference-sensitive species bypassed all head-regeneration defects, suggesting that the Wnt pathway is linked to the emergence of planarian regeneration defects. Our finding that Wnt signalling has multiple roles in the reproductive system of the model species Schmidtea mediterranea raises the possibility that a trade-off between egg-laying, asexual reproduction by fission/regeneration and Wnt signalling drives regenerative trait evolution. Although quantitative comparisons of Wnt signalling levels, yolk content and reproductive strategy across our species collection remained inconclusive, they revealed divergent Wnt signalling roles in the reproductive system of planarians. Altogether, our study establishes planarians as a model taxon for comparative regeneration research and presents a framework for the mechanistic evolution of regenerative abilities.


Venous congestion from brachiocephalic vein stenosis mimicking sclerotic vertebral lesions.
In central venous obstruction, vertebral marrow enhancement (VME) may be seen secondary to collateral venous flow via the vertebral venous plexus.1 There are only sporadic case reports on pseudolesions due to collateral enhancement mimicking sclerotic osseous metastasis. This abnormal vertebral enhancement may lead to erroneous diagnosis of sclerotic metastases or suspicious bone lesion which affect the management and prognosis. We describe a case of brachiocephalic vein obstruction-related vertebral body pseudolesions as identified in contrast-enhanced computed tomography (CECT) scan.


The Role of Molecular Allergens in the Diagnosis of Cat-Pork Syndrome: An Unusual Case Report.
Cat-pork syndrome is a rare condition, with few cases reported in the literature. This syndrome is justified by the homology between serum albumins from cat and pork. Evidence suggests that a primary sensitization to cat serum albumin Fel d 2 occurs, followed by allergic reactions after ingestion of pork meat containing serum albumin Sus s 1. Due to homology between other mammalian serum albumins, reactions with other meats can also be present. We report a well-documented case report of a patient with cat-pork syndrome, with initial mild and non-specific manifestations to well-cooked pork that were overlooked. Component resolved diagnosis was essential to establish the diagnosis, which confirmed the involvement of Fed 2 and Sus s 1, but less relevant in helping to define avoidance diets, since the sensitization profile was not in accordance with clinical manifestations.


Spin susceptibility of noncentrosymmetric heavy-fermion superconductor CeIrSi3 under pressure: 29Si Knight-shift study on single crystal.
We report 29Si NMR study on a single crystal of the heavy-fermion superconductor CeIrSi3 without an inversion symmetry along the c axis. The 29Si Knight-shift measurements under pressure have revealed that the spin susceptibility for the ab plane decreases slightly below T(c), whereas along the c axis it does not change at all. The result can be accounted for by the spin susceptibility in the superconducting state being dominated by the strong antisymmetric (Rashba-type) spin-orbit interaction that originates from the absence of an inversion center along the c axis and it being much larger than superconducting condensation energy. This is the first observation which exhibits an anisotropy of the spin susceptibility below T(c) in the noncentrosymmetric superconductor dominated by strong Rashba-type spin-orbit interaction.