The activities of several detoxication enzymes are differentially induced by juices of garden cress, water cress and mustard in human HepG2 cells.
It has been previously demonstrated in a human-derived hepatoma cell line (HepG2) that juices from cruciferous vegetables protect against the genotoxicity caused by dietary carcinogens. HepG2 cells possess different enzymes involved in the biotransformation of xenobiotics. Therefore, we investigated the effect of cruciferous juices on the activities of CYP 1A and several phase II enzymes in this cell model. For each experiment, 1 x 10(6) cells were seeded on Petri dishes. After 2 days, the juices (0.5-8 microl/ml of culture medium) were added for 48 h prior to cell harvesting. The addition of juice from water cress (Nasturtium officinalis R. Br) significantly increased the activities of ethoxyresorufin-O-deethylase at high doses only and NAD(P)H-quinone reductase in a dose-dependent manner (1.8- and 5-fold, respectively). The addition of juice from garden cress (Lepidum sativum L.) significantly increased the activities of NAD(P)H-quinone reductase and UDP-glucuronosyl-transferase with a maximal effect around the dose of 2 microl/ml juice (1.4- and 1.2-fold, respectively) while the other enzymes were not altered. Mustard (Sinapis alba L.) juice increased the activities of NAD(P)H-quinone reductase (2.6-fold at the dose of 8 microl/ml), and N-acetyl-transferase (1.4-fold at the dose of 8 microl/ml) in a dose-dependent manner while a maximal induction of UDP-glucuronosyl-transferase was obtained with a dose of 2 microl/ml (1.8-fold). These observations show that the three juices have different induction profiles: only water cress acted as a bifunctional inducer by enhancing both phase I and phase II enzymes. As a consequence, each juice may preferentially inhibit the genotoxicity of specific compounds.


Chemodynamics of Polycyclic Aromatic Hydrocarbons and Their Alkylated and Nitrated Derivatives in the Yellow Sea and East China Sea.
The occurrence of continuously released polycyclic aromatic hydrocarbons (PAHs) in marginal seas is regulated by hydrological and biogeochemical processes; however, scarce knowledge is about their derivatives in marine environments. In this study, the dissolved and particulate PAHs and their alkylated/nitrated derivatives (A-PAHs/N-PAHs) in surface seawater of the southwestern Yellow Sea (YS) and northwestern East China Sea (ECS) during September 2022 were comprehensively discussed. Results confirm higher levels of Σ26PAHs (9.3-70 ng/L) and Σ43A-PAHs (13-76 ng/L) than Σ20N-PAHs (0.80-6.6 ng/L). The spatial heterogeneity of contaminants was regulated by substantial riverine runoff and ocean currents. Lagrangian Coherent Structure analysis further revealed the existence of a transport barrier at the shelf break of the southwestern YS where contaminants hardly crossed and tended to accumulate. The relationship between dissolved compounds and chlorophyll a indicated both biodegradation and the biological pump contributed to the depletion of PAHs and A-PAHs from surface seawater while the biological pump was the major driver for N-PAHs, despite their complicated water-particle partition behavior due to variations in physicochemical properties in the presence of nitro groups. Source identification demonstrated that pyrogenic and petrogenic sources dominated the YS and ECS, respectively, while photochemical transformations appeared more active in the YS.


IoT Architecture-Based Mechanism for Digital Transmission of Key Aspects of the Enterprise.
This paper provides an in-depth study and analysis of data transmission in key aspects of the enterprise using internet of things (IoT) technology. IoT technology can provide an effective solution to the integration of enterprise resources and efficiency improvement. If it can be properly introduced into the enterprise, it not only can effectively integrate the enterprise resources in the management but also can significantly improve the efficiency and thus further reduce its operating cost. This paper explores the management application strategy of IoT in the key aspects of digital transmission in enterprises. It can also increase productivity to address labour shortages. Most importantly, because of the internet of things technology, many emerging industries have been derived. In order to achieve this research objective, firstly, based on the in-depth study of the problems of digital transmission of key aspects of the enterprise, this paper evaluates and summarizes the supply chain, safety, efficiency, and quality problems that often occur in the past operation and management of the case enterprise and analyses the main reasons for the formation of the problems and then recognizes the necessity and feasibility of introducing IoT technology and management; secondly, based on the kernel of IoT and industrial IoT technology combined with the main modules of enterprise operation management, using the 5S field management method, we try to build a three-dimensional all-round electrical equipment enterprise IoT management application scheme design system; and finally according to the planning and design rules and management process, we focus on implementing digital transmission network application projects from the enterprise level combining key links of technology and management. This paper studies not only technical innovation but also a revolution in management. The research in this paper will provide a more feasible technical and management design scheme for the application of IoT in enterprises for industry reference.


Rofecoxib-beta-cyclodextrin inclusion complex for solubility enhancement.
Complex formation of rofecoxib and beta-cyclodextrin in aqueous solution and in solid state and the possibility of improving the solubility and dissolution rate of rofecoxib via complexation with cyclodextrin were investigated. Phase solubility studies indicated the formation of an 1:1 complex in solution and the value of apparent stability constant was 769 M(-1). Solid inclusion complexes of rofecoxib and cyclodextrin were prepared by the kneading method in different molar ratios. Differential scanning calorimetry studies indicated the formation of solid inclusion complexes of rofecoxib and cyclodextrin at different molar ratios and the solid complexes exhibited a higher rate of dissolution than the physical mixture and the pure drug.


A Metabolic Activation-Based Chemoproteomic Platform to Profile Adducted Proteins Derived from Furan-Containing Compounds.
Human exposure to widespread furan-containing compounds (FCCs) has drawn much attention due to the high risk of their toxicities. Identifying adducted proteins resulting from the metabolic activation of FCCs is the core to learning the mechanism of FCCs' toxic action. We succeeded in establishing a metabolic activation-based chemoproteomic platform to map FCC-derived protein adducts in cultured primary hepatocytes treated with FCCs and to pinpoint the modification sites, using click chemistry but without alkynylation or azidation of FCCs to be investigated. The proposed platform was systematically verified by biomimetic synthesis, liver microsomal incubation, and primary hepatocyte culture. A mixture of furan, 2-methylfuran, and 2,5-dimethylfuran as model was tested by use of the established platform. A total of hepatic 171 lysine-based adducted proteins and 145 cysteine-based adducted proteins by the reactive metabolites of the three FCCs were enriched and identified (Byonic score ≥ 100). The target proteins were found to mainly participate in ATP synthesis. The technique was also successfully applied to furan-containing natural products. The established platform made it possible to profile covalently adducted proteins, because of potential exposure to a vast inventory of over two million of FCCs documented.


MQCT. I. Inelastic Scattering of Two Asymmetric-Top Rotors with Application to H2O + H2O.
A mixed quantum/classical theory (MQCT) for the inelastic collision of two asymmetric-top rotor molecules is developed. In this method, the quantum state-to-state transitions between the rotational states of molecules (internal) are treated quantum mechanically using the time-dependent Schrodinger equation, whereas their relative translational motion (responsible for scattering) is treated classically, using the average trajectory approach. Two versions of the formula for transition matrix elements are presented: a straightforward approach that uses numerical multidimensional quadrature over all the internal degrees of freedom and a more standard analytic approach that uses the expansion of the PES over the basis set of spherical harmonics. Adaptation to the case of identical molecules scattering is presented and is applied to the rotational excitation of two water molecules, H2O + H2O, using the PES from recent literature. Calculations of collisional excitation from the ground state of the system into a number of low-lying excited rotational states are carried out in a broad range of energies. Analysis of computed opacity functions shows a rather unusual scattering regime, dominated by a strong anisotropic long-range interaction (dipole-dipole). The coupled-states (CS) approximation is tested and found to agree semiquantitatively (within a factor of 2) with the fully coupled version of the method. Differential cross sections for the elastic scattering indicate a very narrow forward scattering peak.


Magnetic resonance of the temporomandibular joint: experience at an Italian university center.
The aim of this investigation was to suggest criteria in order to evaluate magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ). Such criteria have been discussed on the basis of our experience at the Section of Prosthetic Dentistry, Department of Neurosciences, University of Pisa. The study sample was constituted by 135 patients. All subjects underwent bilateral MRI of the TMJs to evaluate disc structure and position, bony structure abnormalities, joint effusion localization and entity. MRI allowed depiction of the articular disc in 98.9% of the TMJs, showing a normal disc structure in 91.1% of the cases and abnormal in 7.7%. The disc-condyle relationship was normal in 46.6% TMJs, while a disc displacement with reduction was revealed in 35.5% cases, a disc displacement without reduction in 16.7% and a posterior disc displacement in 1.5% joints. In the coronal images, the disc was positioned lateral to the condyle in 8.9% of the TMJs and medial in 6.7%. Osseous abnormalities have been found in 177 joints (65.5%), with cases of bony flattening (condyle and/or tuberculum), erosions, subchondral cysts, osteophytosis and sclerosis. T2 sequences showed effusion in 26.7% of the TMJs. These findings suggest that standardized methodology application and well-defined criteria can facilitate MR imaging observations and interpretation as well as the diagnosis of intra-articular pathologies.


Induced pluripotent stem cells in rat models of Parkinson's disease: A systematic review and meta-analysis.
The effects of induced pluripotent stem cells (iPSCs) in 6-hydroxydopamine-lesioned rat models of Parkinson's disease (PD) have been evaluated in multiple studies. However, the results evaluating the effectiveness of iPSCs in animal models of PD are mixed, primarily due to their low statistical power. In the current study, a meta-analysis was performed to describe the treatment effect of unsorted iPSCs on behavioral testing in experimental rat models of PD. Databases searched included PubMed, EMBASE, MEDLINE and the Cochrane Library from inception to March 2017. Data were extracted for rotation behavior tests (induced by amphetamine and apomorphine) and limb function tests. A total of eight studies were included in the current meta-analysis, and iPSCs were identified to be efficacious according to the pooled standardized mean differences (SMDs) for improving amphetamine-induced rotational behavior [SMD, -2.16; 95% confidence interval (95% CI), -2.93, -1.40; P<0.00001] and apomorphine-induced rotational test (SMD, -1.45; 95% CI, -2.16, -0.73; P<0.0001). The pooled evidence indicated that iPSCs improve rotational behavior in rat models of PD. It was concluded that iPSCs provide a potential approach for developing novel treatment strategies for PD, and the results of this meta-analysis may guide future preclinical and clinical studies.


Modification of the cytotoxic activity of mitomycin C by oxygen and ascorbic acid in Chinese hamster ovary cells and a repair-deficient mutant.
The cellular and molecular damage produced by mitomycin C (MMC) in Chinese hamster ovary cells, AA8-4, and a repair deficient mutant of this line, UV-20, was studied by utilizing a system in which oxygen levels could be altered and monitored in solution during acute drug exposures. The cytotoxic activity of MMC decreased from hypoxic conditions to 1% oxygen in solution, while from 1 to 20% there was little change. The relative level of DNA cross-linking in cells was examined under these conditions by alkaline elution and found to increase as cell survival decreased. Utilizing a cell-free assay which detects formation of alkylating species it was confirmed that, while alkylation was observed under aerobic conditions, overall levels increased in the absence of oxygen. The presence of ascorbic acid in the exposure medium (0.284 mM) increased the aerobic but not the hypoxic cytotoxicity of MMC. This resulted in a diminished differential toxicity for cells exposed under aerobic versus hypoxic conditions in the presence of ascorbic acid. When ascorbic acid was present, net alkylation increased under aerobic conditions but was unchanged under hypoxic conditions. One interpretation of these results is that at least two mechanisms of activation of MMC to toxic intermediates may be present in these cells.


Sex-specific action of insulin to acutely increase the metabolic clearance rate of dehydroepiandrosterone in humans.
To test the hypothesis that insulin acutely enhances the metabolic clearance rate (MCR) of dehydroepiandrosterone in humans, the effect of a short-term insulin infusion on the MCR of dehydroepiandrosterone was assessed in 10 men and 7 women. After an overnight fast, dehydroepiandrosterone was infused at 3.47 mumol/h for 6.5 h. At 240 min, a hyperinsulinemic-euglycemic clamp was begun by infusing insulin at 21.5 pmol/kg per min for 2.5 h. MCR of dehydroepiandrosterone was calculated at baseline (210-240 min) and during the insulin infusion (360-390 min). A control study was conducted at least 1 wk later, in which 0.45% saline was substituted for the hyperinsulinemic-euglycemic clamp. During the insulin clamp study, serum insulin rose from 34 +/- 2 to 1084 +/- 136 pmol/liter (P = 0.0001) in men and from 40 +/- 5 to 1357 +/- 175 pmol/liter (P = 0.0003) in women, while serum glucose remained constant in both groups. MCR of dehydroepiandrosterone rose in men during the insulin infusion from 2443 +/- 409 to 3599 +/- 500 liters/24 h (P = 0.003), but did not change during the control saline infusion. In contrast, MCR of dehydroepiandrosterone in women did not change in the insulin clamp study during insulin infusion (2526 +/- 495 liters/24 h at baseline vs. 2442 +/- 491 liters/24 h during insulin infusion; P = 0.78). These findings suggest that insulin acutely increases the MCR of dehydroepiandrosterone in men but not in women.


[Childhood Wells syndrome].
A 12-year-old diabetic girl is reported who developed faintly violaceous nodules on the back of the right thigh. These spread to the posterior aspect of the left thigh and to both legs. She complained of some muscular weakness. A diagnosis of cutaneous polyarteritis nodosa was considered. No blood eosinophilia was detected. Skin biopsy disclosed scattered dermal foci of eosinophilic and granular degeneration of collagen with a palisade of histiocytes and eosinophils in a flame configuration. The lesions did not correspond to the sites of insulin injections. Eight childhood cases of eosinophilic cellulitis were found in the literature, all of them in males. The specificity and meaning of the flame configuration are discussed.


A systematic review of adverse events in randomized trials assessing immune checkpoint inhibitors.
The advent of immune checkpoint-inhibitors (CPI) has transformed treatment for several cancer types. This review was performed to assess the rate of adverse events (AEs) associated with the use of CPI, alone or in combinations. A review of AEs reporting quality was also performed. All publications of Randomized Clinical Trials (RCTs) assessing CPI published before December 2017 were included. To investigate the quality of AEs reporting, a set of items was defined based on the 2004 CONSORT harms extension statement. Rates of Grade 5, serious, and study-withdrawal related AEs were collected in each treatment category. Specific immune related AEs (irAEs) were also collected when available. Pooled estimates of adverse event rates were calculated by using generalized linear mixed model. A total of 35 RCTs including 16,485 patients were included. The overall quality of AEs reporting was satisfactory, but items pertaining to methods of data collection and analysis were infrequently reported. Grade ≥ 3 AEs were reported for 14% (95% CI 12-16) of patients treated with PD(L)-1 inhibitors, 34% (95% CI 27-42) of patients treated with CTLA-4 inhibitors, 55% (95% CI 51-59) of patients on CPI combinations and 46% (95% CI 40-53) of patients on immunotherapy-chemotherapy combination. The profile of irAEs was different among the treatment categories. The use of CPI, especially in combination, is associated with significant rates of Grade ≥ 3 AEs. Healthcare planning should anticipate the expected high number of patients presenting with irAEs in the future.


Genotype by environment interaction for lamb weaning weight in two Norwegian sheep breeds.
Genotype x environment interaction (G x E) effects on live weaning weights of lambs were studied by using the 2 breeds Norwegian White sheep (NWS; heavy, long-tailed) and Spel sheep (Spel; lighter, short-tailed) as genetic groups (G). A total of 37,338 NWS lambs and 30,075 Spel lambs born from 1989 to 1999 on 40 farms that kept both breeds together were included in the analyses. Environment was characterized by farm x year (E). In a mixed linear model framework, significance of the random G x E effect and breed-specific environmental variances were tested by using a log-likelihood approach. Directions and magnitudes of the effect were described through variance component estimates. An across-genotype environmental correlation was also used. There was a significant G x E effect on lamb BW; significant breed differences were found for variance of flock x year effects, indicating different phenotypic plasticities with changing flock x year environments, with the NWS being more sensitive to environmental change. Further, the breed-specific residual variance was greater for NWS, indicating that the effects of environmental variation were larger for the weaning weights of the NWS breed within flock and year. Further, the correlation between flock x year effects for the 2 breeds was significantly different from unity (0.82 +/- 0.02), indicating that the common environment is "perceived" differently in the 2 breeds. The best environment for one breed is not necessarily best for the other breed, and vice versa. Solutions of flock x year effects may be used to describe how environmental characteristics such as climate and topography affect the production of different genotypes, and for clustering of environments, thus facilitating improvement of breeding programs and management schemes for domestic and wild ungulate populations.


Annexin A2 and CD105 expression in pancreatic ductal adenocarcinoma is associated with tumor recurrence and prognosis.
To investigate the value of expression of annexin A2, microvessel density (MVD) and CD105 in pancreatic ductal adenocarcinoma (PDAC) tissues and adjacent normal tissues, immunohistochemical staining was used. The positive expression rate of Annexin A2 and the MVD in pancreatic ductal adenocarcinoma tissues was higher than that in in adjacent normal tissues (p<0.005). Expression of Annexin A2 and MVD correlated with histological grade (p<0.05). MVD of cancers in TNM stage IIb was higher than that in TNM stageI~IIa (p<0.026). Cancerous tissues with Annexin A2 staining grade 3+ had lower MVD than the tissues with the other Annexin A2 staining grade (p<0.05). Patients with high MVD had worse prognosis. However , our study did not confirm Annexin A2 was an independent risk factor for patients with PDAC. We confirmed MVD labeled by CD105 was an independent risk factor for patients with PDAC and had moderate predictive value of prognosis.


Homogeneous cell suspension of Malassezia pachydermatis obtained with an ultrasonic homogenizer.
It is difficult to produce homogeneous cell suspensions of Malassezia pachydermatis, since yeast cells paste up and form many clumps. However, homogeneous fungal suspensions are required for susceptibility examinations and biochemical analyses. Although several types of trials have been carried out using glass homogenizers and many types of agents to obtain homogeneous fungal suspension. They have not yielded good results. We therefore attempted to use an ultrasonic homogenizer to separate clumps of yeast cells into separate individual cells. We succeeded in this fashion in producing homogeneous cell suspensions of M. pachydermatis. These results indicate that an ultrasonic homogenizer can be used to prepare homogeneous fungal suspensions of M. pachydermatis.


Sensory deprivation after focal ischemia in mice accelerates brain remapping and improves functional recovery through Arc-dependent synaptic plasticity.
Recovery after stroke, a major cause of adult disability, is often unpredictable and incomplete. Behavioral recovery is associated with functional reorganization (remapping) in perilesional regions, suggesting that promoting this process might be an effective strategy to enhance recovery. However, the molecular mechanisms underlying remapping after brain injury and the consequences of its modulation are poorly understood. Focal sensory loss or deprivation has been shown to induce remapping in the corresponding brain areas through activity-regulated cytoskeleton-associated protein (Arc)-mediated synaptic plasticity. We show that targeted sensory deprivation via whisker trimming in mice after induction of ischemic stroke in the somatosensory cortex representing forepaw accelerates remapping into the whisker barrel cortex and improves sensorimotor recovery. These improvements persisted even after focal sensory deprivation ended (whiskers allowed to regrow). Mice deficient in Arc, a gene critical for activity-dependent synaptic plasticity, failed to remap or recover sensorimotor function. These results indicate that post-stroke remapping occurs through Arc-mediated synaptic plasticity and is required for behavioral recovery. Furthermore, our findings suggest that enhancing perilesional cortical plasticity via focal sensory deprivation improves recovery after ischemic stroke in mice.


Double-barrelled aorta with tetralogy of Fallot and pulmonary atresia.
We report the first case of double-barrelled aorta associated with tetralogy of Fallot and pulmonary atresia, and we discuss the difficulties in the terminology of this fascinating anomaly.


Clinical associations to abnormal umbilical cord length in Latin American newborns.
Umbilical cord is vital to fetal development and its alterations are related to fetal and neonatal deaths and to late neurological complications. Abnormal cord length has been recognized as the most important cord feature leading to unfavorable outcomes. We aimed to examine the relationship between fetal abnormalities and the length of umbilical cord using the ECLAMC (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas/Latin American Collaborative Study on Congenital Malformations) database. Using ECLAMC case-control registries, we conducted an observational study on the relationship between umbilical cord length and clinical variables such as chromosomal abnormalities and neonatal malformations. Birth registries totaled 61820; of them 3411 had complete cord data. Abnormal length was found in 427, with 174 short (5.10%) cords and 253 long (7.41%) cords. No relation was found between abnormal cord length and gender, parity or parents' age. More abnormal length cords were found than reported in other series; unexpectedly, more long cords were observed in twin gestations. It was observed that among short cords (174), 105 were from newborns with some type of malformation and 69 with no malformation (OR = 2.92, CI (95%) 2.15-3.98, p = 0.0001); of the 253 long cords, 168 had malformation and only 85 did not (OR = 3.80, CI (95%) 2.91-4.96, p = 0.0001). Abnormal cord length is associated with fetal malformation. Further studies are needed to determine the clinical applicability of using this parameter in counseling during prenatal visits.


Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 1): Rate of Crystallization from Cream Containing 20% (w/w) Urea and Evaluation of the Properties of the Deposit.
Two creams containing 20% (w/w) urea and various emulsifiers, a nonionic surfactant (NS) and lecithin (LEC), were prepared, and the rate of crystallization following application of the cream and differences in the properties of the deposits were investigated. Post-application crystallization was slower with the LEC formulation. Differences in the crystals obtained from the two formulations and from a 20% aqueous solution of urea were evaluated by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), powder X-ray-DSC (PXRD-DSC) and Fourier transform infrared spectrophotometry (FT-IR). PXRD and PXRD-DSC measurements showed that the diffraction patterns of both formulations differed from that of urea. The NS formulation provided diffraction peaks for urea and a urea composite, whereas only the urea composite was evident in the LEC formulation. DSC scans of urea showed an endotherm at around 134°C, whereas the deposits from both formulations provided an endotherm 23-25°C below that of urea; the NS formulation also showed a peak at around 140°C. These results indicate a tendency for urea crystallization in the NS formulation. FT-IR measurements showed that both deposits have a urea-based structure. The effects of the LEC formulation components on the physical properties of urea were investigated by PXRD and showed that all diffraction peaks were evenly weakened, suggesting that urea tends to be amorphous and that the formulation impacts post-application urea crystallization. Consequently, the amorphous state of urea can be maintained post-application by optimizing the formulation, thereby increasing the clinical efficacy of the cream.


Salmonella enterica serovar Typhimurium infection induces cyclooxygenase 2 expression in macrophages: involvement of Salmonella pathogenicity island 2.
Salmonella pathogenicity island 2 (SPI-2) is required for intramacrophage survival and systemic infection in mice. We have recently reported that Salmonella enterica causes activation of the protein kinase A (PKA) signaling pathway in a manner dependent on SPI-2, resulting in the upregulation of interleukin-10 expression in macrophages (K. Uchiya et al., Infect. Immun. 72:1964-1973, 2004). We show in the present study the involvement of SPI-2 in a signal transduction pathway that induces the expression of cyclooxygenase 2 (COX-2), an inducible enzyme involved in the synthesis of prostanoids. High levels of prostaglandin E(2) (PGE(2)) and prostacyclin (PGI(2)), which are known to activate the PKA signaling pathway via their receptors, were induced in J774 macrophages infected with wild-type Salmonella compared to a strain carrying a mutation in the spiC gene, located within SPI-2. The increased production of both prostanoids was dependent on COX-2. COX-2 expression was dose dependently blocked by treatment with a specific inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, and the phosphorylation level of ERK1/2 was higher in macrophages infected with wild-type Salmonella compared to the spiC mutant. Taken together, these results indicate that Salmonella causes an SPI-2-dependent ERK1/2 activation that leads to increased COX-2 expression, resulting in the upregulation of PGE(2) and PGI(2) production in macrophages. A COX-2 inhibitor inhibited not only Salmonella-induced activation of the PKA signaling pathway but also growth of wild-type Salmonella within macrophages, suggesting that Salmonella utilizes the COX-2 pathway to survive within macrophages and that the mechanism involves activation of the PKA signaling pathway.


Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis.
To determine whether levels of soluble tumor necrosis factor receptor 55 (sTNFR55), sTNFR75, and interleukin 1 receptor antagonist (IL-1Ra) can differentiate different subtypes of juvenile rheumatoid arthritis (JRA), and to determine if the levels of these proteins correlate with disease activity. Serum sTNFR (55 and 75) and IL-1Ra levels were measured by ELISA in 34 patients with JRA and these values were correlated with disease subtype and activity. Serum sTNFR55 levels were significantly elevated in patients with systemic onset JRA (SoJRA) (mean +/- 2 SD, 2.9 +/- 1.8 ng/ml) (p < or = 0.05) compared to rheumatoid factor positive (RF+) polyarticular JRA (2.1 +/- 0.6), RF-polyarticular JRA (1.5 +/- 0.6), and pauciarticular JRA (1.4 +/- 0.4). There was a trend for elevation of sTNFR75 levels in patients with SoJRA compared to other subtypes (p = 0.08). More patients had elevated levels of sTNFR75 than sTNFR55 (15 vs 7). This was true for all subsets (SoJRA 7 vs 5; polyarticular JRA 4 vs 2; and pauciarticular JRA 4 vs 0). In contrast to sTNFR, IL-1Ra levels were significantly elevated in RF+ polyarticular JRA compared to the other subgroups (p < or = 0.001). We found statistically significant Pearson correlations between (1) sTNFR75 and hemoglobin concentration: and (2) IL-1Ra and number of active joints and number of joints with effusions. The increased serum level of sTNF receptors in SoJRA suggests that TNF is likely more important than IL-1 in systemic inflammation and in particular in SoJRA. Conversely, IL-1 is likely more important in the inflammatory arthritis of JRA and in particular in the pathogenesis of RF+ polyarticular JRA. Our results suggest that cytokines have differing roles in JRA subtypes and likely reflect JRA subtype heterogeneity.


[Use of a genetically labelled strain for the analysis of Yersinia pseudotuberculosis population dynamics in natural soils].
The Rifr mutant of Y. pseudotuberculosis, capable of producing pure cultures in media with a high content of rifampicin, has been used for an accurate quantitation of this microorganism in various kinds of natural (nonsterile) soil in controlled laboratory and field experiments. The main biological characteristics of the mutant have been identical to those of the parent strain. The first experiments have shown that the initially high concentration of Y. pseudotuberculosis in the soil gradually decreases in 2 months. The share of this microorganism in the natural microflora of the soil seems to be rather small, which probably explains the cause of low indices of spontaneous contamination of the soil in nature.


Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome.
Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), even those generally compliant with CPAP therapy, often intermittently discontinue CPAP. Examine the impact of CPAP withdrawal on sleep, sleep disordered breathing (SDB), and daytime function in subjects with varying severity of OSAHS. Forty-two subjects (26M/16 F) with OSAHS (AHI4% = 45.2 ± 35.5/h pretreatment) on CPAP for 4 months were evaluated on the second night of CPAP withdrawal. Sleep architecture, SDB indices, and subjective/objective daytime function were assessed pretreatment, on CPAP therapy, and after CPAP withdrawal. Comparisons were made between pretreatment and CPAP withdrawal for the entire group, and for subgroups of mild/moderate (AHI4% < 30/h, n = 22) and severe (AHI4% > 30/h, n = 20) SDB. Overall, and for mild/moderate subjects, SDB indices returned to pretreatment values on CPAP withdrawal but with fewer apneas and more hypopneas/RERAs. For severe SDB, the event frequency (AI, AHI4%, and RDI) was lower and O2 desaturation was improved on CPAP withdrawal. Across SDB severity, sleep architecture showed lower %REM (15.6% vs 12.9%, P = 0.009) on the CPAP withdrawal compared to pretreatment. Stanford Sleepiness Score, MSLT, and PVT measures were not significantly different between pretreatment and CPAP withdrawal. Over a wide range of SDB severity CPAP withdrawal results in recurrence of SDB, albeit with less severe O2 desaturation. Subjective/objective daytime function returned to pretreatment levels. Sleep architecture changes on CPAP withdrawal (acute SDB) may reflect reduced sleep pressure compared to pretreatment chronic SDB. Our data suggest detrimental effects of even brief withdrawal of CPAP in subjects with both mild and severe OSAHS. Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. SLEEP 2013;36(3):405-412.


Accurate localization of mitral regurgitant defects using multiplane transesophageal echocardiography.
Appropriate patient selection for surgical repair of the mitral valve depends on the specific location and mechanism of regurgitation, which, in turn, has necessitated a more detailed method to accurately describe mitral pathology. This study tests a strategy of using multiplane transesophageal echocardiography to systematically localize mitral regurgitant defects and compares these results with the surgical findings. Fifty patients with mitral regurgitation underwent intraoperative transesophageal echocardiography for the evaluation of mitral pathology and potential repair. Mitral regurgitant defects were localized using a systematic strategy and a simple nomenclature that divides each mitral valve into six sections (three sections per leaflet) and each prosthetic sewing ring into six sections (60 radial degrees = one section). Thirty-nine patients with native mitral valves were studied, for a total of 234 sections evaluated. Eighty-seven of these sections contained regurgitant defects by transesophageal echocardiography (mean number of regurgitant defects per valve, 2.2; range, 1 through 6). There was agreement between the transesophageal echocardiographic and surgical localizations in 96% (224/234; p < 0.0001) of the sections. Eleven patients with prosthetic mitral valves were studied, for a total of 66 sections evaluated. Twenty-three of these sections contained paravalvular leaks by transesophageal echocardiography (mean number of leaks per prosthesis, 2.1; range, 1 through 6). There was agreement between the transesophageal echocardiographic and surgical localizations in 88% (58/66; p < 0.001) of the sections. This transesophageal echocardiographic strategy provides a systematic method to accurately localize mitral regurgitant lesions and has the potential to improve the preoperative assessment of patients with significant mitral regurgitation.


RNA structures with pseudo-knots: graph-theoretical, combinatorial, and statistical properties.
The secondary structures of nucleic acids form a particularly important class of contact structures. Many important RNA molecules, however, contain pseudo-knots, a structural feature that is excluded explicitly from the conventional definition of secondary structures. We propose here a generalization of secondary structures incorporating 'non-nested' pseudo-knots, which we call bi-secondary structures, and discuss measures for the complexity of more general contact structures based on their graph-theoretical properties. Bi-secondary structures are planar trivalent graphs that are characterized by special embedding properties. We derive exact upper bounds on their number (as a function of the chain length n) implying that there are fewer different structures than sequences. Computational results show that the number of bi-secondary structures grows approximately like 2.35n. Numerical studies based on kinetic folding and a simple extension of the standard energy model show that the global features of the sequence-structure map of RNA do not change when pseudo-knots are introduced into the secondary structure picture. We find a large fraction of neutral mutations and, in particular, networks of sequences that fold into the same shape. These neutral networks percolate through the entire sequence space.


Gender effect of hyperuricemia on the development of nonalcoholic fatty liver disease (NAFLD): A clinical analysis and mechanistic study.
Hyperuricemia is a risk factor for nonalcoholic fatty liver disease (NAFLD), however, the effect of gender on the hyperuricemia-related NAFLD development remains unclear. Here, we evaluated the clinical characteristics of NAFLD patients with hyperuricemia, and experimentally recapitulated this condition in male rats in order to gain insights on the possible impact of gender on the development of NAFLD in patients with hyperuricemia. The clinical characteristics of 238 NAFLD patients, together with the impacts of hyperuricemia on the major parameters related to the development of NALFD were analysed. In animal studies, NAFLD with hyperuricemia was induced in male SD rats using high-yeast high-fat diet containing potassium oxonate. The impact of uric acids on liver pathology, and the expression patterns of key molecules involved in the development of NAFLD, including silent information regulator 1 (SIRT1), nuclear factor kappa B subunit p65 (NF-κB p65), fork-head box class O-3a (FOXO3a), androgen receptor (AR), and xanthine oxidase (XO) were analysed. Male NAFLD patients with hyperuricemia displayed more frequent and extensive liver injury than those in female patients. In male rats, hyperuricemia was associated with increased levels of insulin, alanine aminotransferase (ALT) and triglyceride (TG). At the molecular level, hyperuricemia was associated with decreased expression of SIRT1 and its phosphorylation, phosphorylation of FOXO3a, increased expression of AR and XO, and deacetylation of NF-κB P65. Hyperuricemia is a compounding factor for NAFLD, particularly in males. The severer hepatic injury observed in male NAFLD patients may be attributed to the suppression of SIRT1 signalling induced by hyperuricemia.


Various clinical scenarios of primary melanoma of the esophagus: A retrospective 20-year analysis from two university thoracic surgery centers.
Primary melanoma of the esophagus (PME) represents a rare type of gastrointestinal malignancy with an exceptionally poor diagnosis. So far, only few descriptions of PME which satisfactorily summarize their clinical characteristics and prognosis have been published. The aim of our study was to summarize our experience with PME patients. In a group of 1387 patients who underwent esophagectomy due to neoplastic process in the years 2000-2020 in 2 high-volume university thoracic surgery centers, we identified those with confirmed PME diagnosis. Subsequently, their clinical characteristics, imaging and histopathological results were compared. The data regarding the long-term survival were obtained from the Polish National Death Registry. The PME was identified in 4 (0.29%) patients. Three of them (75%) were males. The mean age on admission was 64.3 ±17.5 years. The main symptom in all patients was dysphagia. In 1 patient with the most advanced PME, the clinically relevant weight loss was noted. In 3 patients, Ivor Lewis esophagectomy was performed, and 1 patient underwent McKeown resection. Histopathologic examination revealed a metastasis of lymph nodes only in 1 patient. The average maximum size of tumor was 6.9 ±4.7 cm and all tumors were located in distal part of the esophagus. Two out of those 4 patients are still alive and the longest survival time is 17 years. One patient died due to postoperative massive gastrointestinal bleeding complicated with cardiac arrest and the other one due to progression of PME systemic dissemination 6 months after surgical treatment. The PME is an extremely rare diagnosis. A long-term survival can be achieved with the complete resection. Clinical scenarios of surgically treated PME patients may significantly differ.


Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B virus patients reveals different clinical outcomes depending on the resistance substitutions present.
Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to below the level of detection by PCR (<300 copies/ml) in 21% and 34% of patients by Weeks 48 and 96, respectively. Prior studies showed that virologic rebound due to ETV resistance (ETVr) required preexisting LVDr HBV reverse transcriptase substitutions M204V and L180M plus additional changes at T184, S202, or M250. To monitor for resistance, available isolates from 192 ETV-treated patients were sequenced, with phenotyping performed for all isolates with all emerging substitutions, in addition to isolates from all patients experiencing virologic rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151 (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a more sensitive PCR assay detected many of the emerging changes at baseline, suggesting that they originated during LVD therapy. Only a subset of the changes in ETVr isolates altered their susceptibilities, and virtually all isolates were significantly replication impaired in vitro. Consequently, only 2/187 (1%) patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%) patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other novel substitutions emerged during ETV therapy, but none reduced the susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in LVD-refractory patients, with resistant sequences arising from a subset of patients harboring preexisting LVDr/ETVr variants and with approximately half of the patients experiencing a virologic rebound.


Searching for preventive measures of cardiovascular events in aged Japanese taxi drivers--the daily rhythm of cardiovascular risk factors during a night duty day.
Previous studies have shown that Japanese taxi drivers are exposed to more risk factors and have a higher mortality rate due to cardiovascular disease than other occupational groups. We investigated the effect of night taxi driving with a view to preventing acute events of cardiovascular disease among aged taxi drivers. Twenty-nine taxi drivers (41-67 years old) were examined for urine normetanephrine/creatinine, von Willebrand factor, anti-thrombin III, t-plasminogen activator-plasminogen activator inhibitor 1-complex, hematocrit, blood glucose and blood pressure in the morning and at midnight during a duty day and in the following morning. At the same time, the blood pressure and blood glucose of 46 taxi drivers (43-67 years old) in the morning after a night duty with little sleep and in the morning after daytime work and subsequent night sleep were compared. The results obtained indicate that the aggravation of sympathetic nervous system functions with disturbed circadian rhythms, increased blood coagulation and blood concentration, endothelial injury and the elevation of blood glucose at midnight or the next morning were induced by their night work. These conditions are supposed to favour acute vascular events in aged taxi drivers. Preventive measures considered include social support for anticoagulant food and water intake, short exercise and walking as well as taking a rest and a nap during night work.


Relationship between osteoporosis and cardiovascular disease in postmenopausal women.
In the placebo group of the MORE study, including 2576 postmenopausal women (mean age, 66.5 years), the authors describe a strong linear association between the severity grade of osteoporosis (from low BMD to presence of severe vertebral fractures) and the future risk of cardiovascular events. Accordingly, treatment of postmenopausal osteoporosis should include consideration of measures to prevent adverse cardiovascular outcomes. Observations indicate an inverse association between BMD and the severity of peripheral atherosclerosis in postmenopausal women. The predictive value of osteoporosis and its different severity stages for the risk of acute cardiovascular events remains unknown. Participants were 2576 women (mean age, 66.5 years) assigned to placebo and followed for 4 years in an osteoporosis treatment trial. Those with at least one vertebral fracture or total hip BMD T score < or = -2.5 at baseline were defined as having osteoporosis, whereas those without vertebral fracture and total hip BMD T score between -2.5 and -1 were defined as having low bone mass. The primary outcome for these posthoc analyses was the incidence of adjudicated fatal or nonfatal cardiovascular events. After adjustment for potential confounders, women with osteoporosis had a 3.9-fold (95% CI, 2.0-7.7; p < 0.001) increased risk for cardiovascular events compared with women with low bone mass. Under the same boundaries, a total hip BMD T score < or = -2.5 versus a T score between -2.5 and -1 was associated with a 2.1-fold (95% CI, 1.2-3.6; p < 0.01) increase in risk, whereas presence of at least one vertebral fracture versus no vertebral fracture at baseline was associated with a 3.0-fold (95% CI, 1.8-5.1; p < 0.001) increase in risk. The risk of cardiovascular events increased incrementally with the number and increasing severity of baseline vertebral fractures (both p < 0.001). Postmenopausal women with osteoporosis are at an increased risk for cardiovascular events that is proportional to the severity of osteoporosis at the time of the diagnosis. Treatment of postmenopausal osteoporosis should include consideration of measures to prevent cardiovascular outcomes.


The establishment of structures and processes for the safe and effective clinical placement of nursing students.
Quality education is essential to ensure the continuous provision of safe and competent health professionals entering the workforce. It is dependent on students experiencing an effective clinical placement. This paper discusses a matrix of organisational frameworks, including structures and processes applicable to the supervision of students' clinical learning by health professionals that potentially reduces patients to risk. The matrix is discussed through an analysis of the following: firstly, the legislative structures that regulate the discipline of nursing; secondly the regulatory structures within health sectors and higher education institutions for example, Deeds of Agreement and curriculum documents, and; thirdly those requisite processes, including communication between higher education institutions and within health sectors that ensure understanding of structures and accordingly adequate preparation of staff to undertake supervision. Safe and competent practice is reliant on clearly articulated structures and operationalising processes between the health service sector and higher education institutions that can assist staff and students meet requisite standards of practice.


[Ultrasonography of hips in neonates].
For evaluation of the development of the hip joints in young infants, between Jun., 1988 and Oct., 1991, 522 hips of the infants under 4 months of age were studied by ultrasonography based on the method well described by Graf. The results revealed only 48% of the hips of neonatal group was type I (stable type). But this percentage increased with age: 90% in the group under 2 months of age; 97% in the group under 4 months of age. Compared with the findings of other studies in Europe, the development and the stability of the hips of our neonatal group seemed poorer. But this condition improved much within 2 months after birth. So we concluded that, except the high risk group, the ultrasonographic screening approach should be performed after 2 months of age, but not in neonatal period under considering the cost-benefit.


[Alzheimer disease. Role of beta A4 peptide and cerebral amyloid substance].
Deposition of large quantities of amyloid substance in the walls of the cerebral vessels and in the core of the senile plaques is characteristic of Alzheimer's disease. beta A4 peptide, the main component of the amyloid substance, is a product of a larger amyloid precursor protein which has the structure of a transmembrane receptor and is widely distributed throughout the body. The pathway leading to beta A4 is not yet fully established but could involve lysosomal degradation. It has been suggested that the beta A4 peptide is of neuronal or vascular origin. The beta A4 peptide is found in diffuse deposits in the cortex and cerebellum as well as in the basal ganglia before the classic senile plaques appear, mainly in layer III of the cerebral cortex. These diffuse deposits are devoid of degenerating neurites (i.e. containing abnormally phosphorylated tau protein). The classical senile plaques contain numerous degenerating neurites linking them to the connective network of the cortex. The intellectual deficit is correlated significantly to the density of the classical senile plaques but not to the density of the diffuse deposits. Although a mutation of the gene coding for the beta A4 peptide appears to be sufficient to induce (or accelerate) Alzheimer's disease, this is undoubtedly an exceptional mechanism. Certain mutations involving the beta A4 precursor protein gene increase in vitro the production of beta A4. The molecular and morphological steps leading, from the accumulation of the peptide (which in itself has no clinical expression) to the neurofibrillary pathology of the senile plaques and of the neurones (which are strongly correlated with clinical dementia), remain hypothetical.


[A study of minimally invasive direct coronary artery bypass (MIDCAB): comparison of low risk group and high risk group].
We started to perform MIDCAB for the cases of markedly low cardiac function from June, 1996 and obtained satisfactory results. So we expanded the indications to include only left anterior descending artery (LAD) lesion from June, 1997 and have since performed this operation on 14 cases. The 14 cases of MIDCAB were divided into two groups, Group L consisting of 6 low risk cases: 1 lesion alone without any complications involving other organ before operation and Group H made up of 8 high risk cases: multi branch lesion but rated as high risk because of the extracorporeal circulation being used. Both Group L and Group H were free of operation death and hospital death. In Group L, all the cases underwent operation without blood transfusion, the period of postoperative stay in ICU was not longer than 1 day, on catecholamine was required after operation and complications were not found either. The patency of the graft was 100 percent. The patients were discharged 13.7 days after operation. In Group H, 2 cases required blood transfusion and 3 cases required catecholamine after operation. Complication arising from operative wound were noted in 3 cases. One GEA graft to the right coronary artery and one LITA to the LAD buried in the muscle were occluded. After operation, hospital stay for 23.9 days was required. In Group L, the postoperative course was excellent, so MIDCAB was considered indicated well for this group. In Group H too, the selection of MIDCAB was considered adequate that the risk of conventional CABG is considered much higher.


Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer's disease and other neurodegenerative diseases.
Neuroinflammation is a crucial mechanism in the pathophysiology of neurodegenerative diseases pathophysiology. Cerebrospinal fluid (CSF) YKL-40 - an indicator of microglial activation - has recently been identified by proteomic studies as a candidate biomarker for Alzheimer's disease (AD). Areas covered: We review the impact of CSF YKL-40 as a pathophysiological biomarker for AD and other neurodegenerative diseases. CSF YKL-40 concentrations have been shown to predict progression from prodromal mild cognitive impairment to AD dementia. Moreover, a positive association between CSF YKL-40 and other biomarkers of neurodegeneration - particularly total tau protein - has been reported during the asymptomatic preclinical stage of AD and other neurodegenerative diseases. Albeit preliminary, current data do not support an association between APOE-ε4 status and CSF YKL-40 concentrations. When interpreting the diagnostic/prognostic significance of CSF YKL-40 concentrations in neurodegenerative diseases, potential confounders - including age, metabolic and cardiovascular risk factors, diagnostic criteria for selecting cases/controls - need to be considered. Expert opinion/commentary: CSF YKL-40 represents a pathophysiological biomarker reflecting immune/inflammatory mechanisms in neurodegenerative diseases, associated with tau protein pathology. Besides being associated with tau pathology, CSF YKL-40 adds to the growing array of biomarkers reflecting distinct molecular brain mechanisms potentially useful for stratifying individuals for biomarker-guided, targeted anti-inflammatory therapies emerging from precision medicine.


Positron emission tomography and sentinel lymph node dissection in breast cancer.
Sentinel lymph node dissection (SLND) is emerging as the preferred method of axillary staging for breast cancer patients. To further the use of noninvasive techniques in breast cancer, positron emission tomography (PET) scans have been considered as an alternative axillary staging modality. In order to compare the 2 modalities, we studied 15 invasive breast cancer patients who had undergone a preoperative PET scan before sentinel lymphadenectomy. PET scans were compared to axillary pathology results, which were defined as the greatest diameter of nodal metastases. Primary tumor sizes ranged from 0.5 cm to 5.0 cm (median,1.5 cm) and all were ductal in origin except for 1 invasive lobular and 1 mucinous carcinoma. Ten women had completion axillary dissections. Sentinel lymph node dissection was successful in all patients with completion dissections and no false-negative results. Five patients had sentinel node metastases, but PET scans identified only 1 of these patients, resulting in 4 false-negative PET scans. Missed metastases ranged in size from a micrometastatic focus identified only by immunohistochemistry to a nodal tumor measuring 11 mm in diameter. In addition, 1 woman with a PET-positive axilla was tumor free by SLND and remains free of axillary recurrence 29 months postoperatively. Two women had mediastinal uptake by PET scanning and were found to be tumor free after computerized tomography. The results of this preliminary study suggest that PET scanning using current techniques can be used as an adjunct to SLND rather than as an alternative staging technique.


Risky Sexual Behavior Among Individuals Receiving Buprenorphine/Naloxone Opiate Dependency Treatment: HIV Prevention Trials Network (HPTN) 058.
Understanding the role of opiate dependency treatment in risky sexual behavior could help optimize interventions for people who inject drugs (PWID). We evaluated whether long-term medication-assisted treatment (LT-MAT) of opiate dependency with buprenorphine/naloxone influenced risky sexual behavior among HIV-uninfected PWID and identified predictors of risky sexual behavior. We used data from HPTN 058, a randomized controlled trial of LT-MAT vs. short-term medication-assisted treatment among PWID in China and Thailand. We evaluated associations between randomized opiate dependency treatment group and self-reported risky sexual behaviors within the past month: condomless sex with primary partner, condomless sex with nonprimary partner, multiple partners, and more than 3 sexual acts. We used generalized estimating equations to conduct intention-to-treat, as-treated, and exploratory analyses of these associations. Of 1250 participants included in the analysis, 92% were male, with median age of 34 years (interquartile range 28-39). At baseline, referring to the past month, 36% of participants reported condomless sex with primary partner, 4% reported condomless sex with nonprimary partner, 6% reported multiple sex partners, and 30% reported more than 3 sexual acts. Risky sexual behaviors did not differ significantly between treatment groups at any point. Significant predictors (P < 0.05) of condomless sex with nonprimary partner were history of incarceration and noninjection drug use. Number of needle-sharing partners, noninjection drug use, and higher income were predictors for multiple sexual partners. LT-MAT did not significantly modify risky sexual behavior among HIV-uninfected PWID. Interventions that reduce sexual risk should target PWID with history of incarceration, alcohol use, and needle sharing.


Applications of chlorophyll fluorescence can improve crop production strategies: an examination of future possibilities.
Chlorophyll fluorescence has been routinely used for many years to monitor the photosynthetic performance of plants non-invasively. The relationships between chlorophyll fluorescence parameters and leaf photosynthetic performance are reviewed in the context of applications of fluorescence measurements to screening programmes which seek to identify improved plant performance. The potential role of chlorophyll fluorescence imaging in increasing both the sensitivity and throughput of plant screening programmes is examined. Finally, consideration is given to possible specific applications of chlorophyll fluorescence for screening of plants for tolerance to environmental stresses and for improvements in glasshouse production and post-harvest handling of crops.


Identification of DNA adducts using HPLC/MS/MS following in vitro and in vivo experiments with arylamines and nitroarenes.
Arylamines and nitroarenes are suspected of playing a key role in chemical carcinogenesis. Therefore, the study of DNA adduct formation is an important step to determine the genotoxic potential of these compounds. Calf thymus DNA was modified in vitro by reaction with activated N-hydroxyarylamines: 2-chloroaniline (2CA), 4-chloroaniline (4CA), 2-methylaniline (2MA), 4-methylaniline (4MA), 2,4-dimethylaniline (24DMA), 2,6-dimethylaniline (26DMA), 2-aminobiphenyl (2ABP), 3-aminobiphenyl (3ABP), and 4-aminobiphenyl (4ABP). Female Wistar rats (n = 2) were given a single dose of the above arylamines and their analogous nitro derivatives by oral gavage and sacrificed after 24 h. Hepatic DNA and in vitro modified DNA were hydrolyzed enzymatically to individual 2'-deoxyribonucleosides. Adducts were determined using HPLC/MS/MS by comparison to synthesized standards. The hydrolysis efficiency was monitored by HPLC with UV detection. Each arylamine described above formed adducts to 2'-deoxyguanosine and 2'-deoxyadenosine after in vitro reaction with DNA. DNA adducts were found in rats dosed with 4ABP or with 4-nitrobiphenyl. DNA adducts were not detected in rats dosed with 2CA, 4CA, 2MA, 4MA, 24DMA, 26DMA, 2ABP, 3ABP, 2-chloronitrobenzene, 4-chloronitrobenzene, 2-nitrotoluene, and 4-nitrotoluene. All compounds formed hydrolyzable hemoglobin adducts. Therefore, biologically available N-hydroxyarylamines yielded hemoglobin adducts but not hepatic DNA adducts, except for 4ABP.


Threshold of airway response to inhaled methacholine in healthy men and women.
Threshold of airway response to inhaled methacholine was determined using maximum expiratory partial flow-volume curves in 21 men and 36 women with similar age distribution, all of them healthy nonsmokers. Mean threshold was on average 1.3 doubling dose lower in women than men. There were no sex differences in the increase of maximum expiratory flows after a full inspiration when the airways were constricted by methacholine.


Diabetes insipidus and histiocytosis X: a case of isolated pituitary involvement.
Diabetes insipidus is associated with histiocytosis X in approximately 50% of cases with multiple lesions that involve both intracranial and extracranial structures. Although approximately 8% of cases of diabetes insipidus in children are caused by involvement of the hypothalamus or pituitary infundibulum (or both) by histiocytosis X, diabetes insipidus can be the initial manifestation in many disorders most commonly, intracranial neoplasms. Herein we report a case of isolated histiocytosis X of the pituitary gland in a child for whom medical assistance was sought because of symptoms of diabetes insipidus.


Chemical synthesis of Bi(0.5)Sb(1.5)Te3 nanocrystals and their surface oxidation properties.
Bismuth-antimony-telluride alloy, Bi(0.5)Sb(1.5)Te3, nanocrystals (NCs) have been synthesized by direct chemical solution synthesis, in which the bismuth and antimony precursors, dissolved in a phenyl ether solution and coordinated with dodecanethiol, directly reacted with tellurium in trioctylphosphine. Transmission electron microscopy and X-ray diffraction (XRD) were used for the structure and morphology characterization of these NCs. Their XRD pattern evolution indicated that the reaction temperature plays a critical role in alloying and crystallization of Bi(0.5)Sb(1.5)Te3 NCs. X-ray photoelectron spectrometry was used to study the alloy states and surface oxidation. It is found that the choice of the capping ligands can be important and useful in protecting against the surface oxidation of Bi2Te3-type thermoelectrical nanomaterials.


Improving Health Care Providers' Capacity for Self-Regulated Learning in Online Continuing Pharmacy Education: The Role of Internet Self-Efficacy.
Although Internet-based learning is widely used to improve health professionals' knowledge and skills, the self-regulated learning (SRL) activities of online continuing education in pharmacy are seldom discussed. The main purpose of this study was to explore the relationships between pharmacists' Internet self-efficacy (ISE) and their SRL in online continuing education. A total of 164 in-service pharmacists in Taiwan were surveyed with the Internet Self-Efficacy Survey, including basic ISE (B-ISE), advanced ISE (A-ISE) and professional ISE (P-ISE), as well as the Self-Regulated Learning Questionnaire consisting of preparatory SRL (P-SRL) and enactment SRL (E-SRL). Results of a 1-by-3 (educational levels: junior college versus bachelor versus master) analysis of variance and a 1-by-4 (institutions: community-based versus hospital versus clinic versus company) analysis of variance revealed that there were differences in ISE and SRL among different education levels and working institutions. The hierarchical regression analyses indicated that B-ISE and P-ISE were significant predictors of P-SRL, whereas P-ISE was a critical predictor of E-SRL. Moreover, the interaction of P-ISE × age was linked to E-SRL, implying that P-ISE has a stronger influence on E-SRL for older pharmacists than for younger pharmacists. However, the interactions between age and ISE (A-ISE, B-ISE, and P-ISE) were not related to P-SRL. This study highlighted the importance of ISE and age for increasing pharmacists' SRL in online continuing education.


Stress granules: regulators or by-products?
Cells have to deal with conditions that can cause damage to biomolecules and eventually cell death. To protect against these adverse conditions and promote recovery, cells undergo dramatic changes upon exposure to stress. This involves activation of signaling pathways, cell cycle arrest, translational reprogramming, and reorganization of the cytoplasm. Notably, many stress conditions cause a global inhibition of mRNA translation accompanied by the formation of cytoplasmic condensates called stress granules (SGs), which sequester mRNA together with RNA-binding proteins, translation initiation factors, and other components. SGs are highly conserved in eukaryotes, suggesting that they perform an important function during the stress response. Over the years, many different roles have been assigned to SGs, including translational control, mRNA storage, regulation of mRNA decay, antiviral innate immune response, and modulation of signaling pathways. Most of our understanding, however, has been deduced from correlative data based upon the composition of SGs and only recently have technological innovations allowed hypotheses for SG function to be directly tested. Here, we discuss these challenges and explore the evidence related to the function of SGs.


The Efficacy of Two Trabecular Bypass Stents Compared to One in the Management of Open-Angle Glaucoma.
To compare the outcomes of combined cataract surgery with two trabecular microbypass stents compared to one in patients with open-angle glaucoma. Patients with primary open-angle glaucoma were included. Primary outcome measures were intraocular pressure (IOP), postoperative medications, and postoperative adverse events. The average patient age was 73.2 years. Thirty-nine eyes had phacoemulsification and one stent implanted (Group 1); 30 eyes had phacoemulsification and two stents implanted (Group 2). A significant reduction in mean IOP from baseline to 12 months was noted for both Group 1 (16.67 ± 4.1 mm Hg to 14.45 ± 3.8 mm Hg; p < 0.0251) and Group 2 (18.33 ± 3.99 mm Hg to 14.31 ± 1.8 mm Hg; p < 0.0014). Group 2 had a greater percent decrease in IOP at 12 months than Group 1, but this difference was not statistically significant. Only Group 2 demonstrated a statistically significant reduction in medication burden at 12 months. There were no serious complications in either group thought to be caused by the microbypass stents. Both groups demonstrated a significant reduction in IOP at 12 months. Group 2 showed a greater percent decrease in IOP; however, it was not statistically significant. Only Group 2 demonstrated a statistically significant reduction in medication burden.


Comparative genomics of pyridoxal 5'-phosphate-dependent transcription factor regulons in Bacteria.
The MocR-subfamily transcription factors (MocR-TFs) characterized by the GntR-family DNA-binding domain and aminotransferase-like sensory domain are broadly distributed among certain lineages of Bacteria. Characterized MocR-TFs bind pyridoxal 5'-phosphate (PLP) and control transcription of genes involved in PLP, gamma aminobutyric acid (GABA) and taurine metabolism via binding specific DNA operator sites. To identify putative target genes and DNA binding motifs of MocR-TFs, we performed comparative genomics analysis of over 250 bacterial genomes. The reconstructed regulons for 825 MocR-TFs comprise structural genes from over 200 protein families involved in diverse biological processes. Using the genome context and metabolic subsystem analysis we tentatively assigned functional roles for 38 out of 86 orthologous groups of studied regulators. Most of these MocR-TF regulons are involved in PLP metabolism, as well as utilization of GABA, taurine and ectoine. The remaining studied MocR-TF regulators presumably control genes encoding enzymes involved in reduction/oxidation processes, various transporters and PLP-dependent enzymes, for example aminotransferases. Predicted DNA binding motifs of MocR-TFs are generally similar in each orthologous group and are characterized by two to four repeated sequences. Identified motifs were classified according to their structures. Motifs with direct and/or inverted repeat symmetry constitute the majority of inferred DNA motifs, suggesting preferable TF dimerization in head-to-tail or head-to-head configuration. The obtained genomic collection of in silico reconstructed MocR-TF motifs and regulons in Bacteria provides a basis for future experimental characterization of molecular mechanisms for various regulators in this family.


SecE-depleted membranes of Escherichia coli are active. SecE is not obligatorily required for the in vitro translocation of certain protein precursors.
Membrane vesicles were prepared from Escherichia coli cells in which SecE was depleted to 2% of wild-type membranes. SecE depletion had pleiotropic effects; SecD, SecF, SecG, and SecY were decreased 4-6-fold, whereas SecA was increased about 16-fold over that of wild-type membranes. These membranes were substantially active in the in vitro translocation of proOmpA, which was mediated by the SecA pathway since it was inhibited by azide. Similar substantial translocation activities were observed for proLamB and proLpp in the SecE-depleted membranes. However, the translocation of proPhoA was more severely impaired. These data indicate that SecE may enhance but is not obligatorily required for the translocation of at least certain precursors, and suggest that the effects of the SecE depletion on protein translocation may be precursor-dependent.


Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications.
The polycystic ovary syndrome (PCOS) is a prevalent disorder affecting approximately 6% of women of reproductive age, and is characterized by anovulation and hyperandrogenism. It has also become apparent that a frequent feature of women with PCOS is insulin resistance accompanied by compensatory hyperinsulinemia, and increasing evidence suggests that hyperinsulinemia plays an important role in the pathogenesis of PCOS. This article will review (1) evidence indicating that insulin contributes to the hyperandrogenism of PCOS by stimulating ovarian androgen production and decreasing serum sex hormone-binding globulin (SHBG) concentrations; (2) possible direct effects of hyperinsulinemia on folliculogenesis; (3) the relationship between insulin and adrenal androgens in women; and (4) therapeutic and clinical implications of these findings.


Abnormal Hemoglobins in Turkey.
The presence of HbS was reported in Turkey for the first time in the late fifties by Aksoy et al. This was followed by other reports by the same author revealing the presence of several other abnormal hemoglobins in Turkey. So far up to present 42 abnormal hemoglobins have been identified in the Turkish population. In addition to the studies conducted in Turkey, many European researchers reported their findings in the immigrant Turkish population in their countries. This review tries to cover the tremendous efforts in this field.


Home sweet medical home.
Starting with a solid primary care foundation, the patient-centered medical home has become a hot commodity for making health care more efficient and effective and less fragmented and costly. Whether the enhanced primary care model lives up to its promise is still up for debate, based on the available research. Still, policymakers, payers, and physician practices are increasingly taking the bet.


Evaluation of the Effects of Extremely Low Frequency Electromagnetic Fields on Movement in the Marine Diatom Amphora coffeaeformis.
Published work has shown that population motility in the marine diatom Amphora coffeaeformis can be influenced by externally applied electromagnetic fields (EMFs). Here we report attempts to repeat these experiments, which have been proposed as a model for assessing the effects of EMFs on biological systems. Susceptibility to EMFs was tested using five strains of diatoms on agar plates at a very broad range of field conditions, but no effect on population motility was demonstrated. Exposure period to the EMFs, cell density, and position in the cell cycle had no effect on EMF susceptibility, and the direction and distance moved by the diatoms were not affected by EMFs. When tested after at least a month of preincubation at 20 {mu}T, diatoms of strains #2038, IIIB, and IIIF did show an EMF-induced increase in population motility over control cells (up to ~20%) at conditions predicted by the "ion cyclotron resonance" model, but this effect was ephemeral. Later, IIIB showed a similar increase that was abolished when (1) non-pre-incubated cells were used, (2) the EMF-producing coils were not energized, and (3) even harmonics were used. On observing the response of diatoms to EMFs in real time, a significant increase (~2-fold) in diatom speed over control cells was evident at "ion cyclotron resonance" conditions, using strain #2038 (pre-incubated at 20 {mu}T). The effect was abolished at an even harmonic. We conclude that EMFs can modulate diatom motility, but that the system is, as yet, not consistently reproducible.


Overall Obesity Not Abdominal Obesity Has a Causal Relationship with Obstructive Sleep Apnea in Individual Level Data.
Both obstructive sleep apnea (OSA) and obesity are highly prevalent worldwide, and are intrinsically linked. Previous studies showed that obesity is one of the major risk factors for OSA, but the causality of the relationship is still unclear. The study was to investigate the causal relationships of overall obesity and abdominal obesity with OSA and its quantitative traits. In this case-control study, a total of 7134 participants, including 4335 moderate-to-severe OSA diagnosed by standard polysomnography and 2799 community-based controls were enrolled. Anthropometric and biochemical data were collected. Mendelian randomization (MR) analyses were performed using the genetic risk score, based on 29 body mass index (BMI)- and 11 waist-hip-ratio (WHR)-associated single nucleotide polymorphisms as instrumental variables. The causal associations of these genetic scores with OSA and its quantitative phenotypes were analyzed. Obesity was strongly correlated with OSA in observational analysis (β= 0.055, P = 3.7 × 10-5). In MR analysis, each increase by one standard deviation in BMI was associated with increased OSA risk [odds ratio (OR): 2.21, 95% confidence interval (CI): 1.62-3.02, P = 5.57 × 10-7] and with 2.72-, 4.68-, and 3.25-fold increases in AHI, ODI, and MAI, respectively (all P < 0.05) in men. However, no causal associations were found between WHR and OSA risk or OSA quantitative traits in men and women. Compared to abdominal obesity, overall obesity showed a causal relationship with OSA and its quantitative traits, especially in men.


Are You Missing an Entropion? The Test of Induced Entropion 2.
Entropion is the inward turning of the eyelid. The most common type of entropion is involutional, a combination of eyelid laxity, lower eyelid retractor weakness, and orbicularis oculi override. Unfortunately, the condition can be intermittent and remain undiagnosed, leading to ocular surface damage. In suspected cases, clinicians can use provocation techniques to elicit the condition. These include the forced closure of the eyelids, the tetracaine provocation test, and the test of induced entropion (TIE). The authors present an alternative diagnostic test: the TIE-2. The TIE-2 test is performed by asking the patient to look down while the examiner holds the upper eyelid open and high to prevent downward movement. The patient is then asked to close their eyelids as tightly as possible. An entropion will then be induced. To illustrate the technique, the authors present 2 patients seen in the oculoplastics clinic with symptoms and signs suggestive of intermittent entropion, in whom conventional provocation tests were unsuccessful. In both cases, conventional methods did not provoke an entropion. However, the TIE-2 test successfully induced an entropion, leading to the correct diagnosis and appropriate management. When there is suspicion of intermittent entropion that is not revealed with existing provocation tests, the TIE-2 is a simple and useful diagnostic tool.


Chemotherapy in combination with cytokine-induced killer cell transfusion: An effective therapeutic option for patients with extensive stage small cell lung cancer.
In the past decade of clinical studies, the combination of chemotherapy with cytokine induced killer (CIK) cell transfusion has confirmed a promised efficacy in several types of cancer. CIK cells are a mixture of T lymphocytes, generated from peripheral blood mononuclear cells induced by multiple cytokines. This study was aimed to evaluate the clinical efficacy of chemotherapy combined with CIK- cell therapy in patients with extensive stage small cell lung cancer (ES SCLC). Forty four patients with ES SCLC were enrolled in this study. All the patients received treatment from Oct 2010 to Sep 2013 in the First Affiliated Hospital of Zhengzhou University. Included patients were equally divided into 2 groups according to the treatment strategies. Patients in the combined treatment group received chemotherapy combined with CIK-cell transfusion and patients in the control group received chemotherapy alone. The short-term effects, overall survival (OS), progress free survival (PFS) and therapy-related adverse events were analyzed retrospectively. Short-term efficacy evaluation indicated that the total response rates in the combined treatment group and control group were 40.9% (9/22) and 9.1% (2/22), respectively. There was a significant difference between the two groups (p=0.0339). Furthermore, the PFS of the combined treatment group was significantly longer than that of the control group (8 vs. 4months, P=0.005). No severe side effect was observed after transfusion of CIK cells. These results indicated that chemotherapy combined with CIK-cell immunotherapy might provide a safe and effective treatment for patients with ES SCLC.


Work Productivity Loss in Young Workers Is Substantial and Is Associated With Spinal Pain and Mental Ill-health Conditions.
The aim of this study was to estimate the effect of spinal pain and mental ill-health conditions on work productivity in 22-year-old workers. A cross-sectional design using data from the Raine Study cohort (n = 867) including self-reported work productivity and self-report of health practitioner diagnosed medical conditions. Mean (median, 25th-percentile, 75th-percentile) annualized cost of health-related absenteeism was $AUD1899 ($0, $0, $1738) per worker. Annualized cost of presenteeism was $AUD10,674 ($6573, $4003, $13,087) per worker. Spinal pain and mental ill-health conditions were associated with increased health-related absenteeism, but not presenteeism. Work productivity loss in young workers is a substantial problem needing priority attention. Addressing spinal pain and mental ill-health may improve productivity of this important sector of the workforce.


Acquisition of new protein domains by coronaviruses: analysis of overlapping genes coding for proteins N and 9b in SARS coronavirus.
Acquisition of new proteins by viruses usually occurs through horizontal gene transfer or through gene duplication, but another, less common mechanism is the usage of completely or partially overlapping reading frames. A case of acquisition of a completely new protein through introduction of a start codon in an alternative reading frame is the protein encoded by open reading frame (orf) 9b of SARS coronavirus. This gene completely overlaps with the nucleocapsid (N) gene (orf9a). Our findings indicate that the orf9b gene features a discordant codon-usage pattern. We analyzed the evolution of orf9b in concert with orf9a using sequence data of betacoronavirus-lineage b and found that orf9b, which encodes the overprinting protein, evolved largely independent of the overprinted orf9a. We also examined the protein products of these genomic sequences for their structural flexibility and found that it is not necessary for a newly acquired, overlapping protein product to be intrinsically disordered, in contrast to earlier suggestions. Our findings contribute to characterizing sequence properties of newly acquired genes making use of overlapping reading frames.


High condylectomy and disc repositioning compared to arthroscopic lysis, lavage, and capsular stretch for the treatment of chronic closed lock of the temporomandibular joint.
The article shows the 1-yr results comparing the efficacy of open-surgery high condylectomy and disc repositioning and the arthroscopic procedure of lysis, lavage and capsular stretch in patients with chronic closed lock of the temporomandibular joint (TMJ). Twenty patients with a clinical and radiologic diagnosis of chronic closed lock were randomly chosen to be treated with either open surgery or arthroscopy. Each patient was evaluated with a visual analog scale (VAS) for pain and a mandibular functional impairment questionnaire (MFIQ). The evaluation also included a clinical examination. Each patient was recorded at baseline before surgery and at 1-yr follow-up. Statistical analysis was made to evaluate whether differences in MFIQ, VAS, maximum opening and protrusion, lateral joint tenderness, muscle tenderness, crepitation, and clicking at 1-yr follow-up from baseline were significant. Results were considered statistically significant when P < .05. Both open surgery and arthroscopic surgery reduced pain and improved mandibular function. The severity of pain was significantly reduced in both groups (P = .005). In both the open and arthroscopy groups mandibular function improved significantly (P = .005). The clinical examination showed similar good results for the 2 surgical procedures. At 1-yr follow-up a majority of patients from both the open (80% of the patients) and the arthroscopy (70% of the patients) groups fulfilled the criterion of a cutoff point for maximum interincisal opening of equal or more than 35 mm (P = 0.005); all the patients in both groups fulfilled the criterion of the cutoff point for maximum protrusion of more than 5 mm (P = .007). At 1-yr follow-up, clicking was the same as before surgical procedures; no patient in the open group showed crepitation, but crepitation was found in patients in the arthroscopy group. Joint tenderness and pain on lateral palpation as well as muscle tenderness and pain were reduced in all the cases, disappearing in some of them, but the difference was significant only regarding joint tenderness (open surgery, P = .016; arthroscopy, P = .031). Open-surgery high condylectomy and disc repositioning and the arthroscopic procedure of lysis, lavage and capsular stretch are both effective surgical methods to treat symptomatic patients with a diagnosis of chronic closed lock of the TMJ. Because of the minimally invasive character of the arthroscopic procedure, it should be considered as the first choice in the surgical treatment of the TMJ.


Activation of the gene for atrial natriuretic factor during in vitro cardiac myogenesis by P19 embryonal carcinoma cells.
We examined the transcriptional activity profile of the gene for atrial natriuretic factor (ANF) in mouse embryonal carcinoma P19 cells which had been induced for in vitro cardiac myogenesis. Differentiation was assessed visually, by the degree of spontaneous beating activity, and by the appearance of striated muscle structures detected by immunofluorescence with a myosin heavy chain antibody. Northern blot analysis of RNA isolated at regular intervals throughout the differentiation program revealed abundant cardiac alpha-actin transcripts beginning at Day 6, reaching maximum levels during Days 7 to 8 and declining to low levels by Days 12 to 15. Throughout this period, the transcriptional profile of the ANF gene was similar to that of alpha-actin but at lower levels; thus, in vivo stages of abundant ANF and structural muscle gene transcription were not reached and these gene expression states appear to be uncoupled. Using the more sensitive assay of reverse transcriptase-mediated polymerase chain reactions, we observed the presence of ANF transcripts even in small samples of muscle-induced P19 cells and not in neuron-induced or undifferentiated P19 cells. Induced ANF transcript levels reached about 5-10% that found in adult atrium muscle tissue. ANF gene activity was further corroborated by nuclear transcriptional run-on assays. The P19 stem cell model system will be of value in the study of early events during cardiac muscle commitment and differentiation.


Meningococcal disease in the Middle East: A report from the Global Meningococcal Initiative.
This review details recent findings from the Global Meningococcal Initiative's (GMI) recent meeting on the surveillance and control strategies for invasive meningococcal disease in the Middle East. The nature of case reporting and notification varies across the region, with many countries using bacterial meningitis as an IMD case definition in lieu of meningitis and septicemia. This may overlook a significant burden associated with IMD leading to underreporting or misreporting of the disease. Based on these current definitions, IMD reported incidence remains low across the region, with historical outbreaks mainly occurring due to the Hajj and Umrah mass gatherings. Use of case confirmation techniques also varies in Middle Eastern countries. While typical microbiological techniques, such as culture and Gram staining, are widely used for characterization, polymerase chain reaction (PCR) testing is utilised in a small number of countries. PCR testing may be inaccessible for several reasons including sample transportation, cost, or a lack of laboratory expertise. These barriers, not exclusive to PCR use, may impact surveillance systems more broadly. Another concern throughout the region is potentially widespread ciprofloxacin resistance since its use for chemoprophylaxis remains high in many countries.


Incidence and characteristics of acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest evaluated by non-contrast computed tomography.
The exact epidemiology of acute aortic dissection, including cases of out-of-hospital cardiopulmonary arrest, is unclear. We aimed to investigate the incidence and characteristics of acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest transferred to our institution and validate the related factors to out-of-hospital cardiopulmonary arrest in Stanford type A acute aortic dissection. We retrospectively reviewed the acute-phase computed tomography data of patients with out-of-hospital cardiopulmonary arrest who visited our hospital between 1 January 2015 and 31 December 2017. Among 1011 consecutive patients with out-of-hospital cardiopulmonary arrest, excluding those aged 17 years and younger and exogenous out-of-hospital cardiopulmonary arrest, such as suicide and trauma, 934 underwent computed tomography examination and 71 (7.6%) were diagnosed with acute aortic dissection: 66 with Stanford type A and five with type B acute aortic dissection (out-of-hospital cardiopulmonary arrest group). Seventy-five patients without out-of-hospital cardiopulmonary arrest with Stanford type A acute aortic dissection visited our institution during the same period (non-out-of-hospital cardiopulmonary arrest group). Age, incidence of massive bloody pericardial effusion and massive intrathoracic haemorrhage were significantly higher in the out-of-hospital cardiopulmonary arrest than in the non-out-of-hospital cardiopulmonary arrest group (78 ± 8 years, 72.7% and 24.2% vs. 70 ± 13 years, 26.7% and 1.3%, respectively; all P < 0.01). These variables were independently related to out-of-hospital cardiopulmonary arrest. There may be more patients with acute aortic dissection with out-of-hospital cardiopulmonary arrest than previously thought. Aortic rupture into the pericardial space or thoracic cavity is the major cause of out-of-hospital cardiopulmonary arrest in these cases. Non-contrast computed tomography can be used to diagnose acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest. Our study is one of a few to evaluate the real circumstances surrounding acute aortic dissection and its epidemiology.


Longitudinal Associations between Triglycerides and Metabolic Syndrome Components in a Beijing Adult Population, 2007-2012.
Longitudinal associations between triglycerides (TG) and other metabolic syndrome (MetS) components have rarely been reported. The purpose was to investigate the longitudinal association between TG and other MetS components with time. The longitudinal study was established in 2007 on individuals who attended health check-ups at Beijing Tongren Hospital and Beijing Xiaotangshan Hospital. Data used in this study was based on 7489 participants who had at least three health check-ups over a period of 5-year follow up. Joint model was used to explore longitudinal associations between TG and other MetS components after adjusted for age. There were positive correlations between TG and other MetS components except for high density lipoprotein (HDL), and the correlations increased with time. A negative correlation was displayed between TG and HDL, and the correlation also increased with time. Among all five pairs of TG and other MetS components, the marginal correlation between TG and body mass index (BMI) was the largest for both men and women. The marginal correlation between TG and fasting plasma glucose was the smallest for men, while the marginal correlation between TG and diastolic blood pressure was the smallest for women. The longitudinal association between TG and other MetS components increased with time. Among five pairs of TG and other MetS components, the longitudinal correlation between TG and BMI was the largest. It is important to closely monitor subjects with high levels of TG and BMI in health check-up population especially for women, because these two components are closely associated with development of hypertension, diabetes, cardiovascular disease and other metabolic diseases.


The convergent chemical synthesis of histone H3 protein for site-specific acetylation at Lys56 and ubiquitination at Lys122.
Deposition of (H3-H4)2 tetramers is believed to be the critical step in nucleosome assembly. Site-specific acetylation and ubiquitination of histone H3 have been speculated to synergistically facilitate the formation and deposition of (H3-H4)2 tetramers. Here we report our endeavors toward the first chemical synthesis of homogenous histone H3, which bears Lys56 acetylation and Lys122 ubiquitination, for in vitro biochemical and biophysical studies.


Picosecond pulse radiolysis study of highly concentrated nitric acid solutions: formation mechanism of NO3• radical.
The formation of nitrate radical, NO(3)(•), is observed for the first time directly by picosecond pulse radiolysis of highly concentrated nitric acid solutions. The experimental yield of NO(3)(-) ionization is deduced from the pulse-probe transient absorption measurements in the visible region where this radical absorbs. On the basis of the value of the extinction coefficient of nitrate radical at 640 nm equal to 1300 M cm(-1), the experimental yield of NO(3)(•) at 20 ps is found to be around 0.36 × 10(-7), 1.33 × 10(-7), and 2.85 × 10(-7) mol J(-1) for 1, 3.5, and 7 M nitric acid solutions, respectively. Relative to the dose absorbed by nitric acid by the direct effect, we find an unexpected high formation yield of the nitrate radical within the electron pulse. Therefore, we suggest that the trapping of the positive hole, H(2)O(•+), by NO(3)(-) also contributes to the formation of NO(3)(•) within the electron pulse. Moreover, after the pulse and within 4 ns, the beginning of the reaction of OH(•) radical with undissociated nitric acid is observed for the most concentrated nitric acid solution.


Rapid determination of rivaroxaban in human urine and serum using colloidal palladium surface-assisted laser desorption/ionization mass spectrometry.
Rivaroxaban is a new anticoagulant drug that has recently been introduced for clinical applications. To ensure optimum efficacy while minimizing the risk of toxicity and other adverse effects, a simple and sensitive analytical procedure for monitoring the concentration of rivaroxaban in biological fluids is required. Rivaroxaban was extracted from aqueous solutions by dispersive liquid-liquid microextraction (DLLME). Detection of rivaroxaban was achieved through surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) using colloidal palladium as the SALDI matrix. The calibration curve for rivaroxaban in aqueous solutions was linear over the concentration range from 5 to 500 nM. The limit of detection (LOD) for rivaroxaban at a signal-to-noise ratio of 3 was 2 nM. With a sample-to-extract volume ratio of 200, the enrichment factors were calculated to be 141. This method was successfully applied for the determination of rivaroxaban in human urine and serum samples. The LODs for rivaroxaban in urine and serum were calculated to be 6 nM and 60 nM, respectively. The analysis speed, together with the ease of operation and high sensitivity, allows SALDI-MS method to be particularly suitable for the high-throughput screening of rivaroxaban levels in human urine and serum samples.


Physicochemical characterization and microbiology quality of the Pentadesma butyracea fruit pulp collected from various parks in Benin.
In Benin, P. butyracea fruit pulp undergoes significant post-harvest loss due to its low valorization. The collected fruits in five parklands from a survey of transformer's perception were characterized through their visual observations, the determination of their dimensions and pulp proportions. The nutritional value of pulp was evaluated through its chemical characterization. The results of this study revealed that four shapes (ellipsoid, globular, ovoid, ellipsoid twisted) identify the physical aspect of P. butyracea fruits in the P. butyracea parklands. The average length, diameter at the equator, mass and pulp proportion of fruits were 130.93 mm, 86.98 mm, 125.63 g and 35.79%, respectively. The physicochemical characterization showed that the P. butyracea fruit pulp contained 3.37-3.41 pH, 3.33-4.61% protein, 20.37-20.78% fiber, 2.78-3.57% ash, 6.31-6.51% crude lipid, 85.77-86.47% moisture, 21.54-23.22 mg/mL total phenolics, 0.73-1.03% titratable acidity, 65.10-66.94% carbohydrates, 335.75-338.99 kcal calorie and minerals (Ca, Fe, Zn, Mn). The antioxidant activity result showed that the P. butyracea fruit pulp is a valuable source of antioxidant pigments. Faecal coliforms are not detected in pulps and the aerobic mesophilic bacteria, yeasts and moulds, and Staphylococcus aureus were below detection level in P. butyracea fruit pulps.


Budd-Chiari syndrome: a common complication of Behçet's disease.
The Budd-Chiari syndrome is characterized by venous outflow obstruction of the liver, usually occurring as a consequence of thrombosis of the hepatic veins. Vasculitis is a major component of Behçet's syndrome. The aim of this study was to determine the incidence of hepatic vein thrombosis in patients with Behçet's disease and to estimate the effect of this entity upon the clinical features and course of Behçet's syndrome. During an 8-yr period from 1985 to 1994, from a total of 493 patients with Behçet's disease seen at Hacettepe University Hospital, the incidence and effect of hepatic vein thrombosis on the clinical course of Behçet's syndrome was investigated. The hepatic vein thrombosis in each case was documented by hepatic venography and confirmed by digital subtraction angiography, computed tomography, ultrasonography, and liver biopsy. Coagulation parameters including protein C, protein S, and anti-thrombin III levels were easured in each case. The survival of cases with Behçet's syndrome complicated by Budd-Chiari syndrome and the effect of the Budd-Chiari syndrome on the survival of individuals with Behçet's syndrome were determined using the Kaplan-Meier technique. Of the 493 cases of Behçet's syndrome, 53 (10.8%) were found to have one or more large vessel thrombosis. Of these 53 patients, 14 (26.4%) had hepatic vein thrombosis. Of these 14 patients, 8 had an additional inferior vena cava thrombosis and 4 had portal vein as well as total inferior vena cava thrombosis. Only two patients with isolated hepatic vein thrombosis were identified. These two patients and two additional patients with hepatic vein thrombosis plus thrombosis of the hepatic portion of the inferior vena cava are currently alive. Of the 10 patients with total inferior vena cava and hepatic vein thrombosis (4 also had portal vein thrombosis), all 10 died with a mean survival of 10.3 months. During the same time period, 37 patients obtained from a total of 1494 patients with clinical evidence of either portal hypertension, hepatic venous outflow obstruction or inferior vena caval obstruction without Behçet's syndrome were found to have a Budd-Chiari syndrome. Of these 37 patients, 19 (51%) had an identifiable underlying disorder responsible for their hepatic vein thrombosis. Based upon this experience, it appears as if Budd-Chiari syndrome is a relatively frequent complication of Behçet's disease. When individuals with Behçet's syndrome have BCS, concurrent thrombosis of the portal vein and inferior vena cava are often found, if the patency of these vessels is assessed. The clinical course of patients with Behçet's syndrome complicated by Budd-Chiari syndrome is poor. The extent of the vascular thrombosis within the inferior vena cava rather than the presence of the hepatic vein thrombosis per se is the major determinant of survival.