Scleroderma and malignancy: an epidemiological study.
Although case reports and some patient series suggest an increased risk of cancer among patients with scleroderma, there are no population based studies to support this association. A population based follow up study was therefore carried out of 233 patients with scleroderma from the six-county Uppsala health care region of Sweden for the time period 1955-84. Using the inpatient registry for the Uppsala health care region, all patients with scleroderma were identified. Their unique identification codes were then used to perform a record linkage with the National Cancer Registry. Expected cancer rates were determined using the age and gender specific rates for the Uppsala health care region. The standardised incidence ratio (SIR) for all cancers among these patients was significantly increased (SIR = 2.4; 95% CI = 1.5 to 3.6). The SIRs for lung cancer (SIR = 7.8; 95% CI = 2.5 to 18.2) and non-Hodgkin's lymphoma (SIR = 9.6; 95% CI = 1.1 to 34.5) were also significantly increased. Excluding patients who were diagnosed with cancer within a year of their scleroderma diagnosis resulted in similar findings, though the SIR for non-Hodgkin's lymphoma was no longer statistically significant. Larger population based investigations of cancer risk among patients with scleroderma are needed to confirm these initial findings and to evaluate in greater detail possible cancer risk among these patients.


Nitrogen Codoped Unique Carbon with 0.4 nm Ultra-Micropores for Ultrahigh Areal Capacitance Supercapacitors.
A full understanding of ion transport in porous carbon electrodes is essential for achieving effective energy storage in their applications as electrochemical supercapacitors. It is generally accepted that pores in the size range below 0.5 nm are inaccessible to electrolyte ions and lower the capacitance of carbon materials. Here, nitrogen-doped carbon with ultra-micropores smaller than 0.4 nm with a narrow size distribution, which represents the first example of electrode materials made entirely from ultra-microporous carbon, is prepared. An in situ electrochemical quartz crystal microbalance technique to study the effects of the ultra-micropores on charge storage in supercapacitors is used. It is found that ultra-micropores smaller than 0.4 nm are accessible to small electrolyte ions, and the area capacitance of obtained sample reaches the ultrahigh value of 330 µF cm-2 , significantly higher than that of previously reported carbon-based materials. The findings provide a better understanding of the correlation between ultra-micropore structure and capacitance and open new avenues for design and development of carbon materials for the next generation of high energy density supercapacitors.


Effect of calcitonin gene-related peptide on the cyclic AMP level of isolated mouse diaphragm.
The effect of calcitonin gene-related peptide (CGRP) on the cyclic nucleotide level in isolated mouse diaphragm was investigated. CGRP at concentrations of up to 1 microM caused dose-dependent increases in cyclic AMP levels but had no effect on cyclic GMP levels. At 1 microM, CGRP increased cyclic AMP levels by about 2.7-fold. Moreover, in the presence of phosphodiesterase inhibitor (Ro 20-1724), CGRP still caused even greater dose-dependent increases in cyclic AMP levels. Even in the presence of propranolol, a beta-adrenergic antagonist, CGRP stimulated increased cyclic AMP levels. In addition, specific binding of CGRP was observed in mouse diaphragm. All these results suggest that CGRP increases intracellular cyclic AMP levels via a CGRP receptor but not the beta-adrenergic receptor.


Trypsin clotting time (K-test) in hemophilia A and in hemophilia B1.
In investigations made in 32 patients with haemophilia A and 28 patients with haemophilia B the possibility of utilizing the trypsin clotting time (K-test) was tested in diagnosing both diseases. 23 plasmas of healthy test persons were used as controls and revealed a mean value of the K-test amounting to 24.52 +/- 0.75 seconds. With a mean value amounting to 30.025 +/- 2.88 seconds the K-test was clearly and from a statistical point of view significantly prolonged in hemophilia B contrary to hemophilia A with a slight prolongation amounting to 26.95 +/- 2.03 seconds. Possible causes for the response of the trypsin clotting tie are discussed.


Isolation of yellow fever virus (YFV) from naturally infected Haemagogus (Conopostegus) leucocelaenus (diptera, cukicudae) in São Paulo State, Brazil, 2009.
After detecting the death of Howlers monkeys (genus Alouatta) and isolation of yellow fever virus (YFV) in Buri county, São Paulo, Brazil, an entomological research study in the field was started. A YFV strain was isolated from newborn Swiss mice and cultured cells of Aedes albopictus - C6/36, from a pool of six Haemagogus (Conopostegus) leucocelaenus (Hg. leucocelaenus) mosquitoes (Dyar & Shannon) collected at the study site. Virus RNA fragment was amplified by RT-PCR and sequenced. The MCC Tree generated showed that the isolated strain is related to the South American I genotype, in a monophyletic clade containing isolates from recent 2008-2010 epidemics and epizootics in Brazil. Statistical analysis commonly used were calculated to characterize the sample in relation to diversity and dominance and indicated a pattern of dominance of one or a few species. Hg. leucocelaenus was found infected in Rio Grande do Sul State as well. In São Paulo State, this is the first detection of YFV in Hg. leucocelaenus.


Scaffold effects on osteogenic differentiation of equine mesenchymal stem cells: an in vitro comparative study.
The in vitro viability, osteogenic differentiation, and mineralization of four different equine mesenchymal stem cells (MSCs) from bone marrow, periosteum, muscle, and adipose tissue are compared, when they are cultured with different collagen-based scaffolds or with fibrin glue. The results indicate that bone marrow cells are the best source of MSCs for osteogenic differentiation, and that an electrochemically aggregated collagen gives the highest cell viability and best osteogenic differentiation among the four kinds of scaffolds studied.


Adolescence and the trajectory of alcohol use: introduction to part VI.
Research in the area of adolescent alcohol use is progressing rapidly, as exemplified by the chapters in this section. Basic animal research in rodents has revealed adolescents to be more sensitive than adults to ethanol-induced disruptions in brain plasticity, although adolescents conversely are relatively insensitive to ethanol cues that serve to moderate intake. Risks for excessive alcohol consumption due to genetic background have been shown in primate research to be exacerbated by adverse early life experiences. Studies in clinical populations have revealed neurocognitive deficits evident years following adolescent alcohol abuse, along with evidence that some neural changes may predate adolescent alcohol abuse, whereas others appear to be a consequence of this abuse. Further research is needed to detail determinants and consequences of adolescent alcohol abuse and to identify potential protective factors to diminish the propensity for excessive use of alcohol during this critical developmental period.


Attachment and internalizing behavior in early childhood: a meta-analysis.
Empirical research supporting the contention that insecure attachment is related to internalizing behaviors has been inconsistent. Across 60 studies including 5,236 families, we found a significant, small to medium effect size linking insecure attachment and internalizing behavior (observed d = .37, 95% CI [0.27, 0.46]; adjusted d = .19, 95% CI [0.09, 0.29]). Several moderator variables were associated with differences in effect size, including concurrent externalizing behavior, gender, how the disorganized category was treated, observation versus questionnaire measures of internalizing behavior, age of attachment assessment, time elapsed between attachment and internalizing measure, and year of publication. The association between avoidant attachment and internalizing behavior was also significant and small to moderate (d = .29, 95% CI [0.12, 0.45]). The effect sizes comparing resistant to secure attachment and resistant to avoidant attachment were not significant. In 20 studies with 2,679 families, we found a small effect size linking disorganized attachment and internalizing behavior (observed d = .20, 95% CI [0.09, 0.31]); however, the effect size was not significant when adjusted for probable publication bias (d = .12, 95% CI [-0.02, 0.23]). The existing literature supports the general notion that insecure attachment relationships in early life, particularly avoidant attachment, are associated with subsequent internalizing behaviors, although effect sizes are not strong.


Medial Temporal Lobe Disconnection and Hyperexcitability Across Alzheimer's Disease Stages.
The posteromedial cortex (PMC) and medial temporal lobes (MTL) are two brain regions particularly vulnerable in Alzheimer's disease (AD). We have reviewed the spatiotemporal patterns of amyloid-β and tau accumulation, local MTL functional alterations and MTL-PMC network reconfiguration, and propose a model to relate these elements to each other. Functional and structural MTL-PMC disconnection happen concomitant with amyloid-β plaques and neurofibrillary tau accumulation within these same regions. Ongoing disconnection is accompanied by dysfunctional intrinsic local MTL circuit hyperexcitability, which exacerbates across distinct clinical stages of AD. Our overarching model proposes a sequence of events relating the spatiotemporal patterns of amyloid-β and tau accumulation to MTL-PMC disconnection and local MTL hyperexcitability. We hypothesize that cortical PMC amyloid-β pathology induces long-range information processing deficits through functional and structural MTL-PMC dysconnectivity at early disease stages, which in turn drives local MTL circuit hyperexcitability. Intrinsic local MTL circuit hyperexcitability subsequently accelerates local age-related tau deposition, facilitating tau spread from the MTL to the PMC, eventually resulting in extensive structural degeneration of white and grey matter as the disease advances. We hope that the present model may inform future longitudinal studies needed to test the proposed sequence of events.


Transphyseal anterior cruciate ligament reconstruction in patients with open physes: 10-year follow-up study.
The treatment of anterior cruciate ligament (ACL) injuries in skeletally immature patients is controversial. Current evidence supports the view that surgical techniques restore knee stability and prevent progressive articular damage. However, most of the studies on this topic are small case series or they have short- or medium-term follow-up times. To determine the long-term functional outcomes and secondary complications of transphyseal intra-articular ACL reconstruction with hamstring graft in skeletally immature patients. Case series; Level of evidence, 4. Transphyseal ACL reconstruction with autograft hamstrings was performed in 27 skeletally immature patients. The average age at surgery was 13 years (range, 12-16 years), and the average follow-up time was 10.6 years (range, 10-13 years). Clinical outcomes were assessed with preoperative and final follow-up Tegner, International Knee Documentation Committee (IKDC) subjective, and Lysholm scores. Surgery details, return to sports, and ACL reconstruction failures were collected. The anteroposterior knee laxity was assessed by arthrometry, and the presence of deformities and lower limb length discrepancies were evaluated by radiographs. The presence of degenerative signs on anteroposterior and lateral knee radiographs at final follow-up was also evaluated. Transphyseal ACL reconstruction was performed with vertically oriented tunnels, 7 to 10 mm in diameter, using semitendinosus-gracilis autograft. The average preoperative Tegner, IKDC, and Lysholm scores were 7, 55, and 40, respectively. Significant differences in these scores were observed at the time of the final assessment (Tegner, 6 [P = .026]; IKDC, 94 [P < .001]; Lysholm, 92 [P < .001]). Two patients reported instability during sports activity. Three patients had a rupture of the ACL graft. No leg length discrepancy, axis malalignment, or degenerative changes were observed. The transphyseal ACL reconstruction in skeletally immature patients is a safe option, with high functional and satisfaction results, without significant growth plate damage in this series of patients.


Development of Monopole Interaction Models for Ionic Compounds. Part I: Estimation of Aqueous Henry's Law Constants for Ions and Gas Phase pKa Values for Acidic Compounds.
The SPARC (SPARC Performs Automated Reasoning in Chemistry) physicochemical mechanistic models for neutral compounds have been extended to estimate Henry's Law Constant (HLC) for charged species by incorporating ionic electrostatic interaction models. Combinations of absolute aqueous pKa values, relative pKa values in the gas phase, and aqueous HLC for neutral compounds have been used to develop monopole interaction models that quantify the energy differences upon moving an ionic solute molecule from the gas phase to the liquid phase. Inter-molecular interaction energies were factored into mechanistic contributions of monopoles with polarizability, dipole, H-bonding, and resonance. The monopole ionic models were validated by a wide range of measured gas phase pKa data for 450 acidic compounds. The RMS deviation error and R(2) for the OH, SH, CO2 H, CH3 and NR2 acidic reaction centers (C) were 16.9 kcal/mol and 0.87, respectively. The calculated HLCs of ions were compared to the HLCs of 142 ions calculated by quantum mechanics. Effects of inter-molecular interaction of the monopoles with polarizability, dipole, H-bonding, and resonance on acidity of the solutes in the gas phase are discussed.


Transfer of regulatory toxicology from developed to developing countries.
Over the past two decades, industrialized nations have addressed and attempted to solve the problems of chemical risk through the development of laws, government and private organizations, and specialized manpower. Developing nations are now recognizing that the presence of toxicants in the environment, foods, consumer products, and the workplace can seriously affect human health, the ecology, international relations, and economic activities such as trade and tourism. The design and implementation of regulatory programs in developing countries is hampered by lack of government and public concern, pressure of more urgent needs, vested interests of industry, and lack of adequately trained professionals. These factors have allowed developed nations to sell abroad drugs, pesticides, and other chemicals considered too hazardous for use in their own countries. Conversely, products from developing nations must comply with rigorous standards for acceptance by developed nations. Some of these problems would be lessened by agreement on international chemical control guidelines. Multilateral availability of complete information about chemicals is essential. The coordination of this effort should be in the hands of international organizations and reinforced by bilateral agreements between countries. Appropriate public education and economic incentives at the national level would help in enforcing regulatory toxicology.


Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice.
Sepsis is a common cause of acute renal failure (ARF). The incidence of sepsis increases dramatically after 50 years of age; however, most ARF studies are performed in young mice. We performed two common sepsis models, lipopolysaccharide (LPS) administration and cecal ligation puncture (CLP) in aged mice. We developed a fully treated CLP model in aged mice by treating mice with fluid resuscitation and antibiotics. LPS induced renal injury in aged but not young mice. However, volume resuscitation starting within 6 hours decreased renal injury. We then used this fluid resuscitation scheme, along with antibiotics, to develop a fully treated CLP model in aged mice. Mice subjected to CLP developed functional and histologic ARF and multiple organ damage. Treatment with ethyl pyruvate, even when started 12 hours after surgery, decreased serum creatinine, tubular damage, and multiple organ injury at 24 hours. Ethyl pyruvate decreased plasma tumor necrosis factor-alpha (TNF-alpha), and kidney mRNA for TNF alpha, tissue factor, and plasminogen activator inhibitor-1 (PAI-1), and increased mRNA for urokinase-like plasminogen activator. CLP in aged mice causes functional and histologic changes consistent with human ARF. A single dose of ethyl pyruvate inhibits renal and multiple organ damage, and is still effective when given 12 hours after surgery.


Effect of clinical condition and mycophenolate mofetil on plasma retinol, α-tocopherol and β-carotene in renal transplant recipients.
Plasma antioxidant vitamins (retinol, α-tocopherol, β-carotene) were measured to establish the influence of clinical condition and mycophenolate mofetil (MMF) treatment on the nutritional status of renal transplant recipients. In 106 adult patients plasma vitamins were measured and 24-h diet history questionnaires were conducted. The MMF influence on plasma vitamins was verified in 61 patients. The current dietary intakes of vitamins in daily food rations were lower than recommended. Plasma retinol was lower in patients suffering from gastrointestinal disorders (1.25 ±0.48 mg/l vs. 1.55 ±0.70 mg/l) and inversely associated with aminotransferases activity (p = 0.019) and creatinine clearance (p = 0.021). Retinol concentrations were positively associated with plasma creatinine (p = 0.027) and pharmacokinetic parameters of MMF phenyl glucuronide. β-Carotene concentrations were higher in women (0.39 ±0.46 mg/l vs. 0.28 ±0.23 mg/l; p = 0.041) and when MMF was co-administered with cyclosporine vs. tacrolimus (0.45 ±0.62 mg/l vs. 0.25 ±0.19 mg/l). Plasma α-tocopherol correlated negatively with the mycophenolic acid pre-dose concentration (p = 0.027) and was significantly lower in patients treated with calcineurin inhibitors (8.90 ±5.23 mg/l vs. 12.25 ±5.62 mg/l). A positive correlation was observed between α-tocopherol levels and aspartate aminotransferase (p = 0.006). In multivariate regression aspartate aminotransferase and MMF treatment significantly influenced retinol (p < 0.001). The MMF treatment was associated with significantly lower retinol concentrations. The gastrointestinal disorders occurrence in MMF-treated patients may cause a decrease in retinol absorption. Diet adjustment and/or vitamin A supplementation should be considered.


Ankyrin-B regulates Cav2.1 and Cav2.2 channel expression and targeting.
N-type and P/Q-type calcium channels are documented players in the regulation of synaptic function; however, the mechanisms underlying their expression and cellular targeting are poorly understood. Ankyrin polypeptides are essential for normal integral membrane protein expression in a number of cell types, including neurons, cardiomyocytes, epithelia, secretory cells, and erythrocytes. Ankyrin dysfunction has been linked to defects in integral protein expression, abnormal cellular function, and disease. Here, we demonstrate that ankyrin-B associates with Cav2.1 and Cav2.2 in cortex, cerebellum, and brain stem. Additionally, using in vitro and in vivo techniques, we demonstrate that ankyrin-B, via its membrane-binding domain, associates with a highly conserved motif in the DII/III loop domain of Cav2.1 and Cav2.2. Further, we demonstrate that this domain is necessary for proper targeting of Cav2.1 and Cav2.2 in a heterologous system. Finally, we demonstrate that mutation of a single conserved tyrosine residue in the ankyrin-binding motif of both Cav2.1 (Y797E) and Cav2.2 (Y788E) results in loss of association with ankyrin-B in vitro and in vivo. Collectively, our findings identify an interaction between ankyrin-B and both Cav2.1 and Cav2.2 at the amino acid level that is necessary for proper Cav2.1 and Cav2.2 targeting in vivo.


[Lymphatic manifestation forms in the terminal phase of chronic myelocytic leukemia].
A blastic transformation in chronic myeloic leukaemia (CML) is reported, which, on the one hand, is characterized by the "lymphoid" feature of blasts and, on the other hand, by the appearance of great lymph node swellings. The clear distinction from (secondary) malignant lymphomas may be difficult. The inclusion of such forms of blastic transformation in CML is based on cytogenetic findings. Their non-granulocytic or "lymphoid" nature emerges from their cytological behavior. The fact that these lymphoid transformations respond to vincristin and prednison emphasize that their recognition as special entities is justified. They also demonstrate that the neoplastic process in CML may not only involve myelopoietic but pluripotent stem cells as well.


The Kinetic Changes of Systemic Inflammatory Factors during Bevacizumab Treatment and Its Prognostic Role in Advanced Non-small Cell Lung Cancer Patients.
Background: Bevacizumab combined with chemotherapy is still one of the standard options for treatment of advanced non-small cell lung cancer (NSCLC) patients without driver mutations. Serum inflammatory factors, representing the systemic immune status, are shown to have complicated relationships with tumor angiogenesis, and proved to be associated with survival of advanced NSCLC patients. However, the information from the baseline factors is relatively limited, which cannot reflect the dynamic changes of systemic immune status during bevacizumab treatment. We, thus, attempted to evaluate longitudinal kinetics of systemic inflammatory factors during treatment of bevacizumab and to explore their predictive role in treatment response and patient outcomes in advanced NSCLC. Method: Systemic inflammatory factors (neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), neutrophil×platelet/lymphocyte (SII) and lymphocyte/monocyte (LMR)) and clinical variables were collected and analyzed from 161 advanced NSCLC patients treated with bevacizumab. Mixed effect regression models were first performed for longitudinal analysis of the changes of serum inflammatory factors during bevacizumab treatment. Then, univariate and multivariate Cox models were used for overall survival (OS) and progression free survival (PFS) analyses to determine the independent prognostic factors. Results: In the first 6 cycles of bevacizumab treatment, patients with complete response/partial response (CR/PR) had a -0.11, -0.066, -0.15, and 0.073 change every 2 cycles in transformed NLR (95%CI: -0.19--0.03, p=0.008), PLR (95%CI: -0.12--0.013, p=0.015), SII (95%CI: -0.23--0.05, p<0.001) and LMR (95%CI: 0.049-0.14, p=0.036), respectively, compared to patients with progressive disease (PD). With respect to analysis of the longitudinal changes before progression, patients experienced a significant increase in transformed NLR (Coef=0.09, 95%CI: 0.019-0.17, p=0.014), PLR (Coef=0.05, 95%CI: 0.002-0.10, p=0.04), and SII (Coef=0.091, 95%CI: 0.015-0.17, p=0.019), but a decrease in transformed LMR (Coef=-0.08, 95%CI: -0.14-0.018, p=0.012). On multivariate Cox model analyses, decrease of LMR (HR=0.62, 95% CI: 0.4-0.96, p=0.033) was shown to be the independent risk factor for PFS; and low level of baseline LMR (HR=0.4, 95% CI: 0.17-0.94, p=0.036), increase of NLR (HR=2.36, 95%CI: 1.25-4.44, p=0.008), and decrease of LMR (HR=0.42, 95%CI: 0.18-0.97, p=0.041) were the independent risk factors for death. Conclusion: The activation of systemic immune status evaluated by the kinetic changes of serum inflammatory factors was associated with good response to bevacizumab; however, the suppressive status may indicate the resistance to bevacizumab. Dynamic changes of systemic inflammatory factors also had prognostic value in predicting outcomes of advanced NSCLC patients treated with bevacizumab.


Treatment of dysmenorrhoea and premenstrual syndrome with non-steroidal anti-inflammatory drugs.
The menstrual cycle is associated with 2 potentially incapacitating events: dysmenorrhoea and premenstrual syndrome. Although substantial evidence has accumulated to indicate that excessive endometrial production of prostaglandin F2 alpha is the major underlying cause of painful menstruation, correspondingly little is currently known about the basic aetiology of the premenstrual syndrome. Non-steroidal anti-inflammatory drugs have been used to alleviate the discomfort of both entities, and while these agents have come to assume a primary role in the treatment of dysmenorrhoea, a body of evidence substantiating their efficacy in premenstrual syndrome has yet to be developed.


[Effect of ecoimmunonutrition on gut barrier function in rats with systemic inflammatory response syndrome].
To explore the effect of ecoimmunonutrition on gut barrier function in rats with systemic inflammatory response syndrome (SIRS). Rat models of SIRS were established by injecting lipo polysaccharide (LPS) via the tail vein. Sixty male Sprague-Dawley rats were randomly divided into 4 groups. One of the four enteral nutrition formulas (standard EN, immunonutrition, econutrition, ecoimmunonutrition) was given to each group respectively for 7 days. Serum D-lactate, diamine oxidase (DAO), ratio of urinary lactulose to mannitol (L/M) were measured on day 1 before LPS injection (D (-1)) and day 1, 3, 6 after LPS injection (D(+1), D (+3), D (+6)). After 7 days of treatment,the level of serum D-lactate in econutrition group was significantly lower than those in standard EN or immunonutrition group (P< 0.05), and the level of serum D-lactate in all above three groups were significantly higher compared with ecoimmunonutrition group (P< 0.01). The level of serum DAO in standard EN group was higher than those in other three groups(P< 0.01). The L/M was increased in all the groups on D(+1), D(+3). It fell back to the basic level on D(+6)) in all the groups.The L/M in immunonutrition group was lower than those in other groups on D (+1) (P< 0.05), and it was higher in standard EN group than those in other groups on D (+3) (P< 0.01). Ecoimmunonutrition, a enteral nutrition composed of immune-enhanced nutrient and ecologic, may protect the gut barrier function more effectively in rats with SIRS.


The SOS Regulatory Network.
All organisms possess a diverse set of genetic programs that are used to alter cellular physiology in response to environmental cues. The gram-negative bacterium Escherichia coli induces a gene regulatory network known as the "SOS response" following exposure to DNA damage, replication fork arrest, and a myriad of other environmental stresses. For over 50 years, E. coli has served as the paradigm for our understanding of the transcriptional and physiological changes that occur after DNA damage. In this chapter, we summarize the current view of the SOS response and discuss how this genetic circuit is regulated. In addition to examining the E. coli SOS response, we include a discussion of the SOS regulatory networks found in other bacteria to provide a broad perspective on the mechanism and diverse physiological responses that ensueto protect cells and maintain genome integrity.


Floquet Engineering of Correlated Tunneling in the Bose-Hubbard Model with Ultracold Atoms.
We report on the experimental implementation of tunable occupation-dependent tunneling in a Bose-Hubbard system of ultracold atoms via time-periodic modulation of the on-site interaction energy. The tunneling rate is inferred from a time-resolved measurement of the lattice site occupation after a quantum quench. We demonstrate coherent control of the tunneling dynamics in the correlated many-body system, including full suppression of tunneling as predicted within the framework of Floquet theory. We find that the tunneling rate explicitly depends on the atom number difference in neighboring lattice sites. Our results may open up ways to realize artificial gauge fields that feature density dependence with ultracold atoms.


Regioselective HON-addition of bifunctional hydrazone oximes to Pt(IV)-bound nitriles.
Treatment of trans-[PtCl(4)(RCN)(2)](R = Me, Et) with the hydrazone oximes MeC(=NOH)C(R')=NNH(2)(R' = Me, Ph) at 45 degrees C in CH(2)Cl(2) led to the formation of trans-[PtCl(4)(NH=C(R)ON=C(Me)C(R')=NNH(2))(2)](R/R' = Me/Ph 1, Et/Me 2, Et/Ph 3) due to the regioselective OH-addition of the bifunctional MeC(=NOH)C(R')=NNH(2) to the nitrile group. The reaction of 3 and Ph(3)P=CHCO(2)Me allows the formation of the Pt(II) complex trans-[PtCl(2)(NH=C(Et)ON=C(Me)C(Ph)=NNH(2))2](4). In 4, the imine ligand was liberated by substitution with 2 equivalents of bis(1,2-diphenylphosphino)ethane (dppe) in CDCl(3) to give, along with the free ligand, the solid [Pt(dppe)(2)]Cl(2). The free iminoacyl hydrazone, having a restricted life-time, decomposes at 20-25 degrees C in about 20 h to the parent organonitrile and the hydrazone oxime. The Schiff condensation of the free NH(2) groups of 4 with aromatic aldehydes, i.e. 2-OH-5-NO(2)-benzaldehyde and 4-NO(2)-benzaldehyde, brings about the formation of the platinum(II) complexes trans-[PtCl(2)(NH=C(Et)ON=C(Me)C(Ph)=NN=CH(C(6)H(3)-2-OH-5-NO(2))2](5) and trans-[PtCl(2)(NH=C(Et)ON=C(Me)C(Ph)=NN=CH(C(6)H(4)-4-NO(2))2](6), respectively, containing functionalized remote peripherical groups. Metallization of 5, which can be considered as a novel type of metallaligand, was achieved by its reaction with M(OAc)(2).nH(2)O (M = Cu, n= 2; M = Co, n= 4) in a 1:1 molar ratio furnishing solid heteronuclear compounds with composition [Pt]:[M]= 1:1. The complexes were characterized by C, H, N elemental analyses, FAB+ mass-spectrometry, IR, 1H, 13C[1H] and (195)Pt NMR spectroscopies; X-ray structures were determined for 3, 4 and 5.


Longer Leukocyte Telomere Length Predicts Stronger Response to a Workplace Sugar-Sweetened Beverage Sales Ban: An Exploratory Study.
Shorter leukocyte telomere length (LTL) is associated with increased risk of a number of metabolic diseases including insulin resistance and the development of type 2 diabetes mellitus. Shorter LTL is also associated with stress reactivity suggestive of a possible role for LTL to predict response to behavioral interventions. However, few studies have evaluated how interventions, such as weight loss or dietary changes, are associated with LTL changes or whether LTL can predict behavioral responses to interventions. We evaluated metabolic changes in relation to LTL changes and LTL at baseline in a cohort of at-risk adults in response to a 10-mo workplace-based sugar-sweetened beverage (SSB) intervention. At baseline, metabolic health and LTL measurements were assessed through standard blood draws on 212 participants. Multivariable linear regression models were used to assess changes in anthropometrics, SSB consumption, and 13 blood-based metabolic risk factors, in relation to LTL at baseline and changes in LTL. Longer LTL at baseline was associated with decreases in SSB consumption over the 6-mo follow-up period (B = -29.67; P = 0.04). Slower LTL attrition rates were associated with decreases in waist circumference (B = -0.27; P = 0.03), HDL cholesterol (B = -0.20; P = 0.05), and apoA1 (B = -0.09; P = 0.01). Longer LTL at baseline predicted a favorable overall response to a behavioral intervention: decreases in SSB consumption. Abdominal adiposity losses paralleled slower declines in LTL suggestive of overall health benefits, but we found differences in the relations between metabolic changes and LTL at baseline compared with LTL attrition rates. Longer LTL may be a proxy marker of a positive behavioral response.This trial was registered at clinicaltrials.gov as NCT02585336.


Discovery and characterization of family 39 glycoside hydrolases from rumen anaerobic fungi with polyspecific activity on rare arabinosyl substrates.
Enzyme activities that improve digestion of recalcitrant plant cell wall polysaccharides may offer solutions for sustainable industries. To this end, anaerobic fungi in the rumen have been identified as a promising source of novel carbohydrate active enzymes (CAZymes) that modify plant cell wall polysaccharides and other complex glycans. Many CAZymes share insufficient sequence identity to characterized proteins from other microbial ecosystems to infer their function; thus presenting challenges to their identification. In this study, four rumen fungal genes (nf2152, nf2215, nf2523, and pr2455) were identified that encode family 39 glycoside hydrolases (GH39s), and have conserved structural features with GH51s. Two recombinant proteins, NF2152 and NF2523, were characterized using a variety of biochemical and structural techniques, and were determined to have distinct catalytic activities. NF2152 releases a single product, β1,2-arabinobiose (Ara2) from sugar beet arabinan (SBA), and β1,2-Ara2 and α-1,2-galactoarabinose (Gal-Ara) from rye arabinoxylan (RAX). NF2523 exclusively releases α-1,2-Gal-Ara from RAX, which represents the first description of a galacto-(α-1,2)-arabinosidase. Both β-1,2-Ara2 and α-1,2-Gal-Ara are disaccharides not previously described within SBA and RAX. In this regard, the enzymes studied here may represent valuable new biocatalytic tools for investigating the structures of rare arabinosyl-containing glycans, and potentially for facilitating their modification in industrial applications.


Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin.
Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was -3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only -1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV.


Effect of whole body vibration training on quadriceps strength, bone mineral density, and functional capacity in children with hemophilia: a randomized clinical trial.
The objective was to evaluate the effects of whole body vibration training on quadriceps strength, bone mineral density, and functional capacity in children with hemophilia. Thirty children with hemophilia with age ranging from 9 to 13 years were selected and randomly assigned to either the study group that received whole body vibration training (30-40 Hz, 2-4 mm of peak-to-peak vertical plate displacement for 15 minutes/day, 3 days/week/ 12 weeks) plus the conventional physical therapy program or the control group that performed a conventional physical therapy program only. Outcomes included quadriceps strength, bone mineral density, and the functional capacity. Children in the study group showed a significant improvement in all outcomes compared with the control group. The quadriceps peak torque after treatment was 70.26 and 56.46 Nm for the study and control group, respectively (p⟨0.001). The lumbar spine bone mineral density after treatment was 0.85 and 0.72 g/cm2 for the study and control group, respectively (p⟨0.001). The functional capacity after treatment was 325 and 290 m for the study and control group, respectively (p=0.006). Whole body vibration training is an effective modality in increasing quadriceps strength, bone mineral density, and functional capacity in children with hemophilia.


A novel bipyridine-based hexadentate tripodal framework with a strong preference for trigonal prismatic co-ordination geometries.
The synthesis of the novel ligand tris(2,2'-bipyrid-6-yl) methanol (L(1)) is described. Co-ordination of the ligand to the first row transition metals (Mn(2+)-Zn(2+)) as well as Cd(2+) showed that the ligand formed complexes close to trigonal prismatic in geometry in the solid state. Analysis of the geometry of the co-ordination spheres showed varying degrees of trigonal prismatic and octahedral character. For each d-electron configuration, this could be related to the relative differences in ligand field stabilisation energies for the two geometries.


A new selective method for isolation of Haemophilus species.
Chocolate agar with teicoplanin disk (30 micrograms) was used for the isolation of Haemophilus strains. Fifty strains of 3 Haemophilus species grew as well in the inhibition zones of teicoplanin disks as on teicoplanin containing selective plates, whereas Gram-positive bacteria failed to form colonies. This selective method proved especially advantageous when Haemophilus strains were isolated from mixed bacterial cultures of 665 specimens.


Predicting early discharge from hospital after liver transplantation (ERDALT) at a single center: a new model.
Limited information related to Liver Transplantation (LT) costs in South America exists. Additionally, costs analysis from developed countries may not provide comparable models for those in emerging economies. We sought to evaluate a predictive model of Early Discharge from Hospital after LT (ERDALT = length of hospital stay ≤ 8 days). A predictive model was assessed based on the odds ratios (OR) from a multivariate regression analysis in a cohort of consecutively transplanted adult patients in a single center from Argentina and internally validated with bootstrapping technique. ERDALT was applicable in 34 of 289 patients (11.8%). Variables independently associated with ERDALT were MELD exception points OR 1.9 (P = 0.04), surgery time < 4 h OR 3.8 (P = 0.013), < 5 units of blood products consumption (BPC) OR 3.5 (P = 0.001) and early weaning from mechanical intubation OR 6.3 (P = 0.006). Points in the predictive scoring model were allocated as follows: MELD exception points (absence = 0 points, presence = 1 point), surgery time < 4 h (0-2 points), < 5 units of BPC (0-2 points), and early weaning (0-3 points). Final scores ranged from 0 to 8 points with a c-statistic of 0.83 (95% CI 0.77-0.90; P < 0.0001). Transplant costs were significantly lower in patients with ERDALT (median $23,078 vs. $28,986; P < 0.0001). Neither lower patient and graft survival, nor higher rates of short-term re-hospitalization and acute rejection events after discharge were observed in patients with ERDALT. In conclusion, the ERDALT score identifies patients suitable for early discharge with excellent outcomes after transplantation. This score may provide applicable models particularly for emerging economies.


Dynamic Behavior of Nano-Size Dust Particles in a Magnetic Field Channel.
Removal of very small dust from indoor public spaces, such as metro subway stations, is a challenge. A large proportion of subway dust, particularly that of submicron sizes, contains iron compounds. This study sought to understand the dynamic behavior of such fine iron dust in a magnetic field. The computer aided fluid dynamics (CFD) calculation revealed that the design and configuration of a rectangular flow channel with magnets determine the dynamic motion of particles. An attractive magnetic emitter arrangement produced higher magnetic flux density than a repulsive arrangement. Additional ferromagnetic wire mesh inserted into the duct channel could provide a more systematic magnetic field and collect more dust. The field gradient for 0.3 mm thick wire was more than twice that of 0.5 mm wire. The provision of a magnetic field could contribute a 20% increase in 100 nm particle collection and an increase of 5% in 10 nm.


Dizinc enzyme model/complexometric indicator pairs in indicator displacement assays for inorganic phosphates under physiological conditions.
A dizinc phosphohydrolase enzyme model complex employing the dinucleating ligand 2,6-bis-[(bis-pyridin-2-ylmethyl-amino)methyl]-4-methylphenol (L1) was tested for binding to a series of 11 commercially available complexometric indicators in aqueous N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer at pH 7.4, with the aim of determining the applicability of these indicators in indicator displacement assays (IDAs) under physiological conditions. Dissociation constants (Kd) were determined for 11 indicator-Zn2L1 complexes, spanning 2 orders of magnitude from 2.8 x 10(-4) M (alizarin red S) to 2.7 x 10(-6) M (bromo pyrogallol red). Phosphate and pyrophosphate were tested for their ability to displace bound indicator and produce a detectable colorimetric response. Three indicators (bromo pyrogallol red, mordant blue 9, and zincon) complex to Zn2L1 to form an indicator displacement assay selective for pyrophosphate over phosphate. Because selection of an indicator/analyte pair having appropriate relative Kd values is critical for their successful application in IDAs, the binding data for these 11 indicators should assist their extension to IDAs for other analytes.


The value of routine biopsy during percutaneous kyphoplasty for vertebral compression fractures.
Percutaneous kyphoplasty (PKP) is now widely performed to treat VCF, which is usually caused by osteoporosis. Previous researches have reported unsuspected malignancies found by biopsy. However, the safety and cost-effective profiles of routine biopsy during PKP are unclear. The purpose of this study was to evaluate the feasibility of routine biopsy during PKP in treatment of VCF. Ninety-three patients (September 2007-November 2010) undergoing PKP without biopsy were reviewed as the control group. One hundred and three consecutive patients (November 2010-September 2013) undergoing PKP with biopsy of every operated vertebral level were prospectively enrolled as the biopsy group. The rate of unsuspected lesions was reported, and the severe adverse events, surgical duration, cement leakage rate and pain control were compared between the two groups. No statistically significant differences were found between the two groups, regarding the severe adverse events, surgical duration, cement leakage rate and pain control. Four unsuspected lesions were found in the biopsy group, three of which were malignancies with a 2.9% (3/103) unsuspected malignancy rate. The economic analysis showed that routine biopsy was cost-effective in finding new malignancies comparing with a routine cancer screening campaign. Routine biopsy during PKP was safe and cost-effective in finding unsuspected malignancies. We advocate routine biopsy in every operated vertebral level during PKP for VCF patients.


Targeting transcription factor STAT3 for cancer prevention and therapy.
Signal Transducers and Activators of Transcription (STATs) comprise an important class of transcription factors that have been implicated in a wide variety of essential cellular functions related to proliferation, survival, and angiogenesis. Among various STAT members, STAT3 is frequently overexpressed in tumor cells as well as tissue samples, and regulates the expression of numerous oncogenic genes controlling the growth and metastasis of tumor cells. The current review briefly discusses the importance of STAT3 as a potential target for cancer therapy and also provides novel insights into various classes of existing pharmacological inhibitors of this transcription factor that can be potentially developed as anti-cancer drugs.


The 10,000 Immunomes Project: Building a Resource for Human Immunology.
There is increasing appreciation that the immune system plays critical roles not only in the traditional domains of infection and inflammation but also in many areas of biology, including tumorigenesis, metabolism, and even neurobiology. However, one of the major barriers for understanding human immunological mechanisms is that immune assays have not been reproducibly characterized for a sufficiently large and diverse healthy human cohort. Here, we present the 10,000 Immunomes Project (10KIP), a framework for growing a diverse human immunology reference, from ImmPort, a publicly available resource of subject-level immunology data. Although some measurement types are sparse in the presently deposited ImmPort database, the extant data allow for a diversity of robust comparisons. Using 10KIP, we describe variations in serum cytokines and leukocytes by age, race, and sex; define a baseline cell-cytokine network; and describe immunologic changes in pregnancy. All data in the resource are available for visualization and download at http://10kimmunomes.org/.


A rare form of hypothyroidism.
Secondary hypothyroidism is extremely rare. In the majority of cases, there is a genetic (gene mutations) or structural (mass effect or infiltration) basis for central hypothyroidism, and there is simultaneous deficiency of other adenohypophysial hormones. Isolated deficiency of thyrotropin is even rarer. This report features the case of a woman who had isolated thyrotropin deficiency, with the remainder of the anterior pituitary hormones being normal. The various causes of central hypothyroidism and the role of the thyrotropin-releasing hormone test are briefly described.


Injectable and Self-Healing Dynamic Hydrogels Based on Metal(I)-Thiolate/Disulfide Exchange as Biomaterials with Tunable Mechanical Properties.
Despite numerous strategies involving dynamic covalent bonds to produce self-healing hydrogels with similar frequency-dependent stiffness to native tissues, it remains challenging to use biologically relevant thiol/disulfide exchange to confer such properties to polymeric networks. Herein, we report a new method based on Metal(I) [Au(I) or Ag(I)] capping to protect thiolates from aerial oxidation without preventing thiolate/disulfide exchange. Dynamic hydrogels were readily prepared by injecting simultaneously aqueous solutions of commercially available HAuCl4 and 4-arm thiol-terminated polyethylene glycol [(PEGSH)4], resulting in a network containing a mixture of Au(I)-thiolate (Au-S) and disulfide bonds (SS). While the dynamic properties of the hydrogel were closely dependent on the pH, the mechanical properties could be easily tuned by adjusting (PEGSH)4 concentration and amount of Au-S, as judged by dynamic rheology studies. Permanent Au-S/SS exchange at physiological pH conferred self-healing behavior and frequency-dependent stiffness to the hydrogel. In addition, in vitro studies confirmed that Au-based dynamic material was not cytotoxic to human dermal fibroblasts, demonstrating its potential use as a medical device. Dynamic hydrogels obtained using Ag(I) ions demonstrated that the exchange reaction was not affected by the nature of the Metal(I) capping. Finally, this efficient thiolate capping strategy offers a simple way to produce injectable and self-healing dynamic hydrogels from virtually any thiol-containing polymers.


[The clinical significance of PIVKA-II determination in patients with hepatocellular carcinoma: a comparative study with alpha-fetoprotein].
The changes in the plasma level of PIVKA-II (Protein Induced by Vitamin K Absence or Antagonist-II) following the treatment or progress of the disease was studied in 60 patients with hepatocellular carcinoma. The positivity rate determined by the changes in PIVKA-II was 58.4 percent (35/60 cases) and was about the same as those reported so far, all of which were obtained by a single determination of PIVKA-II. Plasma PIVKA-II was elevated in 61.9 percent (13/21 cases) of alpha-fetoprotein negative patients and it was almost identical with the overall positivity rate. In parallel with serum alpha-fetoprotein, the plasma level of PIVKA-II was decreased after the surgery or transcatheter arterial embolization and was increased when the recurrence or progress of the disease was observed. Furthermore, the nonspecific elevation of PIVKA-II due to the associated liver cirrhosis or chronic hepatitis was infrequent compared with that of alpha-fetoprotein. In 18 cases positive with both PIVKA-II and alpha-fetoprotein, a close correlation (R = 0.91) was observed between the changes of these markers during the progress or treatment of the disease. Thus, it was suggested that determination of PIVKA-II in blood might be useful not only in the diagnosis but in monitoring the progress or the effectiveness of treatments in hepatocellular carcinoma.


Suicidal ideation and attentional biases in children: An eye-tracking study.
Despite theoretical and empirical evidence for a heighted responsiveness to signals of social-threat in suicidal individuals, no studies to date have examined whether this responsiveness might also manifest in the form of specific biases in attention to interpersonal stimuli. The current study, therefore, examined the presence and nature of attentional biases for facial expressions of emotion in children with and without a history of suicidal ideation (SI). Participants were 88 children (44 with a history of SI and 44 demographically and clinically matched controls without such history) recruited from the community. The average age of children was 9.26 years (44.3% female; 67.0% Caucasian). Children's history of SI was assessed via structured interviews with children and their parent. Attentional biases were assessed using a dot probe task and included fearful, happy, and sad facial stimuli and focused on eye tracking and reaction time indices of attentional bias. Children with a history of SI exhibited significantly greater gaze duration toward fearful faces. The findings appeared to be at least partially independent of children's history of major depression or anxiety disorders or their current depressive or anxious symptoms. The study is limited by its cross-sectional design, which precludes any causal conclusions regarding the role of attentional biases in future suicide risk. Our results suggest that children with a history of SI exhibit biases in sustained attention toward socially-threatening facial expressions. Pending replications, these findings might represent a new avenue of suicide risk assessment and intervention.


Intramuscular Lipoma of the Flexor Hallucis Brevis MuscleA Case Report.
An intramuscular lipoma is a deep-seated, rare, benign mesenchymal tumor that arises in skeletal muscle. These soft-tissue masses are rarely reported in the foot. We describe an unusual case of an intramuscular lipoma of the flexor hallucis brevis muscle. A review of the literature revealed only one previous report of this lesion in the foot.


Glycyrrhizic acid as the antiviral component of Glycyrrhiza uralensis Fisch. against coxsackievirus A16 and enterovirus 71 of hand foot and mouth disease.
The radices of Glycyrrhiza uralensis Fisch. and herbal preparations containing Glycyrrhiza spp. have been used for thousands of years as an herbal medicine for the treatment of viral induced cough, viral hepatitis, and viral skin diseases like ulcers in China. Glycyrrhizic acid (GA) is considered the principal component in Glycyrrhiza spp. with a wide spectrum of antiviral activity. The present study attempt to validate the medicinal use of Glycyrrhiza uralensis for hand, foot and mouth disease (HFMD) and further to verify whether GA is an active antiviral component in the water extract of Glycyrrhiza uralensis. Radices of Glycyrrhiza uralensis Fisch. were extracted with hot water. The chemical contents of the extract were profiled with HPLC analysis. The antiviral activity of the extract and the major components was evaluated against infection of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) on Vero cells. The cytopathic effect caused by the infection was measured with MTT assay. Infectious virion production was determined using secondary infection assays and viral protein expression by immunoblotting analysis. The extract at 1000 μg/ml suppressed EV71 replication by 1.0 log and CVA16 by 1.5 logs. The antiviral activity was associated with the content of GA in the extract since selective depletion of GA from the extract by acid precipitation resulted in loss of antiviral activity. In contrast, the acid precipitant retained antiviral activity. The precipitant at a concentration of 200 μg/ml inhibited EV71 and CVA16 replication by 1.7 and 2.2 logs, respectively. Furthermore, GA dose-dependently blocked viral replication of EV71 and CVA16. At 3 mM, GA reduced infectious CVA16 and EV71 production by 3.5 and 2.2 logs, respectively. At 5mM, CVA16 production was reduced by 6.0 logs and EV71 by 4.0 logs. Both EV71 and CVA16 are members of Enterovirus genus, time-of-drug addition studies however showed that GA directly inactivated CVA16, while GA anti-EV71 effect was associated with an event(s) post virus cell entry. This study validated the medicinal usefulness of radices Glycyrrhiza uralensis against the etiological agents of HFMD. In addition to the identification of GA as the antiviral component of Glycyrrhiza uralensis against EV71 and CVA16 infection, this study also reveals that GA inhibits EV71 and CVA16 with distinct mechanisms.


'Blueprint' for creating classroom facilities in teaching hospitals.
Classroom facilities in teaching hospitals have evolved from simple rooms with blackboards to sophisticated amphitheaters with high-tech audiovisual equipment. This article presents a "blueprint," which was used in an osteopathic hospital, to renovate existing space into classrooms that are conducive to learning.


The nicotinic receptor in the rat pineal gland is an alpha3beta4 subtype.
The rat pineal gland contains a high density of neuronal nicotinic acetylcholine receptors (nAChRs). We characterized the pharmacology of the binding sites and function of these receptors, measured the nAChR subunit mRNA, and used subunit-specific antibodies to establish the receptor subtype as defined by subunit composition. In ligand binding studies, [3H]epibatidine ([3H]EB) binds with an affinity of approximately 100 pM to nAChRs in the pineal gland, and the density of these sites is approximately 5 times that in rat cerebral cortex. The affinities of nicotinic drugs for binding sites in the pineal gland are similar to those at alpha3beta4 nAChRs heterologously expressed in human embryonic kidney 293 cells. In functional studies, the potencies and efficacies of nicotinic drugs to activate or block whole-cell currents in dissociated pinealocytes match closely their potencies and efficacies to activate or block 86Rb+ efflux in the cells expressing heterologous alpha3beta4 nAChRs. Measurements of mRNA indicated the presence of transcripts for alpha3, beta2, and beta4 nAChR subunits but not those for alpha2, alpha4, alpha5, alpha6, alpha7, or beta3 subunits. Immunoprecipitation with subunit-specific antibodies showed that virtually all [3H]EB-labeled nAChRs contained alpha3 and beta4 subunits associated in one complex. The beta2 subunit was not associated with this complex. Taken together, these results indicate that virtually all of the nAChRs in the rat pineal gland are the alpha3beta4 nAChR subtype and that the pineal gland can therefore serve as an excellent and convenient model in which to study the pharmacology and function of these receptors in a native tissue.


Reciprocal recombination products of VK-JK joining reactions in human lymphoid cell lines.
The recombination process that joins a VK to a JK segment of an immunoglobulin gene generates a second, reciprocal recombination product called f fragment. In this second product the regions flanking the VK and JK segments in the germline are joined in a head to head fashion. We now analysed f fragments in the human lymphoid cell lines Daudi, JI and IARC/BL41. All three f fragments contain JK1 flanks; the VK derived moiety of f Daudi and f41 could be traced back to known germline VK genes. There is a precise head to head joining of the heptanucleotide signal sequences in f Daudi and fJI while in f41 six nucleotides are present between the signal sequences. In contrast to the VK-JK recombination products, the f fragments were found to lack somatic mutations. The structures of the f fragments are discussed in the context of the VK-JK rearrangement mechanism.


Behavioral aspects of development of eating behavior and nutrition status.
Studies on the development of eating behavior in rural India indicated that mothers of young children made food choices that fit into their budgets, and were also influenced by new information. Their choices were still immersed in traditional beliefs, some of which had positive effects on nutrition. Specific childrearing behaviors influenced positive deviance in the growth and psychosocial development of infants and preschoolers. A life-cycle approach to the development of eating behavior that deciphers needs at each stage and linkages between stages is necessary. Cost-benefit needs to be considered when devising strategies for future intervention programs.


Calculation of the probability of survival for trauma patients based on trauma score and the injury severity score model in fatemi hospital in ardabil.
Trauma, in addition to economic and social costs, is the fourth cause of death in the world and in the year 2000 alone, it led to the death of more than 6000000 people. In Iran, Trauma has the first burden of disease and also needs a long medical surveillance. The aim of this study was to evaluate the outcome of trauma cases using the trauma score and the injury severity score (TRISS) model and then comparing this with the results of a major trauma outcome study (MTOS) carried out in the US. This study is a retrospective, descriptive and analytical study on 1000 patients aged 2 - 82 years old with closed or penetrating traumas staying at Ardebil Fatemi hospital. In this study, injury severity score (ISS), revised trauma score (RTS), and TRISS were calculated and patients' viability ratios were obtained. The results showed that 714 patients (71.4%) were male and 286 patients (28.6%) female with the mean age of 35.68 years. In this study 45 (4.5%) and 955 patients (95.5%) had penetrating and blunt traumas, respectively, whereby the head and neck were the most prevalent (74%) areas of injury. The most common reason for these traumas was, accident with vehicles with 670 cases (67%), which resulted in hospitalization. From this group, ninety-seven cases (9.7%) died in the hospital. From these results, calculations of ISS and RTS were 15.50 ± 11.31 and 7.49 ± 0.79, respectively. According to the calculation of the TRISS model, 91.5% of trauma victims should be survived, while only 90.3% survived practically. We can conclude that the surveillance presented to our injured group probably had some defects that need to be revised in therapeutic services to enhance survival requirements.


Control of glycogen synthesis in health and disease.
Investigations in our laboratory have shown that the activity of glycogen synthase phosphatase in the liver is shared by at least two functionally distinct proteins: a G-component, which is tightly associated with glycogen particles, and a soluble S-component. Most preparations of glycogen synthase-b that are isolated from the liver of fed glucagon-treated animals require the presence of both components in order to be converted to synthase-a. The G-component is subject to control mechanisms that do not affect the S-component. Its activity is strongly inhibited by phosphorylase-a. This feature explains why glycogen synthesis and glycogenolysis do not normally occur simultaneously, except in the glycogen-depleted liver, where a futile cycle may occur. Experiments in vitro have shown that a minimal glycogen concentration is required to ensure the interaction between the G-component and phosphorylase-a. The G-component is also selectively inhibited by Ca2+, and the magnitude of this inhibition depends markedly on the glycogen concentration. The latter inhibition is probably one of the mechanisms by which cyclic adenosine monophosphate (cAMP)-independent glycogenolytic agents achieve the inactivation of glycogen synthase in the liver. Glucocorticoid hormones and insulin are required for the induction and/or maintenance of the G-component in the liver. During the development of the fetal rat, glucocorticoids induce the G-component in the liver. This is an essential event in the glucocorticoid-triggered deposition of glycogen in the fetal liver. A functional adrenal cortex is also required in the adult animal to prevent a loss of the capacity for hepatic glycogen storage during starvation. The latter capacity depends on the concentration of functional G-component in the liver. Chronic diabetes causes a similar functional loss. However, the effect of glucocorticoids is not mediated by a putative secretion of insulin.


[The role of paracetamol in transition reactions of alpha-nitrogen and oxidative stress in the liver].
Paracetamol (Acetaminophen, PC) is metabolized in liver to N-acetyl-p-benzoquinon-imine (NAPQI), that is in turn conjugated by glutathione S-transferase with glutathione. NAPQI inhibits the respiratory chain. It may cause a 90% decrease of ATP concentration in mitochondria of hepatocytes. The oxidation of paracetamol to quinine form can also generate free radicals. Both above mentioned processes, can injure the mitochondria and cells. There have not been found in accessible literature any data dealing with paracetamol influence on the process elimination of the alpha nitrogen in the liver. The ATP concentration decline may lead to disturbances in mitochondrial enzymes. There are discrepant data of the role of free radicals in the mechanism of toxic action of paracetamol.


Steric control of a bridging ligand for high-nuclearity metallamacrocycle formation: a highly puckered 60-membered icosanuclear metalladiazamacrocycle.
A novel S4-symmetric icosanuclear manganese metalladiazamacrocycle was synthesized using a pentadentate ligand, N-3-phenyl-trans-2-propenoylsalicylhydrazide (H3L), that has a rigid and bulky terminal N-acyl group. A 20 cyclic repeat of an--(Mn-N-N)--linkage resulted in a highly puckered diaza-bridged 60-membered icosanuclear metallamacrocycle. The steric interaction between the ligands in the cyclic system leads to five consecutive Mn(III) centers in a chemically different--(Mn(A)Mn(B)Mn(C)Mn(D)Mn(E))--environment, with the chiralities of the metal centers being in a rather complicated--(LambdaLambdaDeltaLambdaLambda)(DeltaDeltaLambdaDeltaDelta)--sequence.


Fatigue and quality of life of women with multiple sclerosis: a randomized controlled clinical trial.
The aim of this study was to determine the effects of aquatic exercise on fatigue and the quality of life in women with multiple sclerosis (MS). This randomized controlled clinical trial was carried out in a multiple sclerosis clinic in Iran, where 37 outpatient women with MS were randomized into an exercise group (N.=18) and a control group (N.=19). In the exercise group, aquatic exercise was performed for 45 minutes, 3 times per week for 8 weeks. The control group did not receive any interventions (aquatic exercise) and were asked to maintain their normal treatments. The severity and perception of fatigue and quality of life (QoL) were measured using the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Multicultural Quality of Life Index (MQLIM) questionnaires. The repeated measure ANOVA demonstrated significant effects of aquatic exercise on the changes in the scores of physical and psychosocial fatigue perception, QoL, and fatigue severity (P=0.001). However, its effect was not significant for cognitive fatigue perception (P>0.05). General linear models show that the percentages of variation, as explained by the aquatic exercises, were highest in the QoL and the physical and psychosocial fatigue perceptions. Aquatic exercise can improve the QoL and decrease fatigue severity and fatigue perception, specifically in the physical and psychosocial domain for MS patients. However, it was not effective in improving cognitive fatigue perception.


Coexisting polymorphisms of P2Y12 and CYP2C19 genes as a risk factor for persistent platelet activation with clopidogrel.
Coexisting polymorphisms of the genes affecting clopiogrel resistance may influence platelet activation. In 105 patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention, platelet function was measured and registered as closure time in the test with collagen and adenosine diphosphate (CADP-CT). Patients were followed for 12 months for death or recurrent myocardial infarction (MI). Genotyping revealed 7 carriers of both the C allele of P2Y12 and A allele of CYP2C19 (group 1), 14 carriers of the T allele of P2Y12 and A allele of CYP2C19 (group 2), 17 carriers of the C allele of P2Y12 and G allele of CYP2C19 (group 3) and 67 carriers of the T allele of P2Y12 and G allele of CYP2C19 (controls). The median CADP-CT value was significantly lower in group 1 than in group 2 or 3 (p<0.01) or controls (p<0.002), but did not differ between group 2 or 3 and controls. There were 2 cardiovascular deaths and 4 MI during follow-up, and the median CADP-CT value was lower in these patients (p=0.09). Coexisting, rather then single, polymorphisms of different genes may be related to persistent platelet activation while on clopidogrel, which raises concern about harm in patients with ACS.


Acute pericarditis: diagnostic cues and common electrocardiographic manifestations.
Acute pericarditis (AP) is basically a clinical diagnosis. Although specific electrocardiographic (ECG) manifestations may indeed point to its diagnosis, sole reliance on such findings in isolation of the clinical setting, however, is often the common pitfall that could lead to a misguided diagnosis. We briefly review the anatomy of the pericardium and the pathophysiology of pericarditis to highlight common signs and symptoms as well as clinical findings that may assist in the diagnosis of AP. We also feature the characteristic evolution of its ECG manifestations and point out some of its typical and atypical features to help better differentiate AP from commonly confused conditions.


THE CASE OF A 14-YEAR-OLD BOY WHO EXPERIENCED ANAPHYLAXIS DUE TO JELLYFISH (MASTIGIAS PAPUA) INGESTION.
We report a case of jellyfish allergy diagnosed via an oral food challenge. A 14-year-old boy had no history of jellyfish stings and had been eating commercially available jellyfish products twice yearly for the past 5-6 years. Five minutes after eating a commercially available boiled jellyfish product (100g), he experienced nausea, wheezing, and erythema and had visited our hospital. We suspected an anaphylactic reaction and treated him with intramuscular adrenaline injection, corticosteroid and antihistamine infusions, volume resuscitation, and salbutamol sulfate inhalation, which resulted in an improvement of the symptoms. One-month later in our hospital, we administered an oral food challenge of the same boiled jellyfish product bought at the same grocery store to the patient. After ingesting 14g of boiled jellyfish, he experienced erythema, wheezing, nausea, and abdominal pain. Several reports have described anaphylaxis caused by the ingestion of jellyfish, but the allergens in jellyfish have not been analyzed. A skin prick test for poly-gamma-glutamic acid (PGA) which is a component of jellyfish stings was negative. This suggests that he was sensitized to some allergen other than PGA via a route different from that of jellyfish sting. Our skin prick test for several kinds of edible jellyfish suggests that allergenicity may be different for different jellyfish.


The Location and Severity of Preoperative Subchondral Bone Marrow Lesions Were Not Associated With Inferior Postoperative Outcomes After Medial Unicompartmental Knee Arthroplasty or Total Knee Arthroplasty.
Inferior outcomes for medial unicompartmental knee arthroplasty (UKA) patients with preoperative medial tibial bone marrow lesions (BMLs) were recently reported. The purpose of this study was to compare the location and severity of BML on postoperative outcomes after medial UKA and TKA using a larger sample size and more rigorous magnetic resonance imaging (MRI) evaluation. BML were graded on preoperative MRIs from 174 UKAs performed between 2009 and 2013 using the MRI Osteoarthritis Knee Score criteria. Grading was performed by a single evaluator blinded to the patient's outcome. MRIs from a matched group of 174 TKAs were then evaluated. Preoperative and postoperative Knee Society Knee Scores, Pain Scores, and Function Scores (FSs) were then compared between UKA and TKA patients based on the location and severity of BMLs. Overall medial-side BML severity (sum of tibia, femur, and patellar grades) did not affect Pain Score or FS; however, UKA and TKA patients with more severe BMLs had greater preoperative-to-postoperative gains in Knee Society Knee Scores (P = .05). When evaluating individual regions, UKA patients with more severe medial tibial BML had significantly greater gains in FS than those without BML, whereas the opposite was true for TKA patients (P = .02). Similarly, UKA and TKA patients with patellar lesions had greater gains in FS than those without BML (P = .05). Medial femoral BML did not appear to affect outcomes for either UKA or TKA patients. Medial tibial BMLs were not associated with inferior outcomes. Clinically, these results suggest that BMLs should not be considered a contraindication for medial UKA.


Addiction-related interactions of pregabalin with morphine in mice and humans: reinforcing and inhibiting effects.
The gabapentinoid pregabalin is a rapid-acting anxiolytic and analgesic, possibly suitable in supervised opioid detoxification. However, clinicians have been cautious in using it because of its unknown addictive risk and rising number of mortalities after pregabalin self-medication in opioid abusers. Here, we studied interactions of pregabalin and morphine on reward functions of the dopamine system in mice and the efficacy of pregabalin on withdrawal in opioid addicts. After the treatment of mice with pregabalin and morphine, we used electrophysiology to study neuroplasticity in midbrain slices, self-administration and conditioned place preference tests to investigate the rewarding potential of pregabalin and naloxone-precipitated morphine withdrawal to evaluate opioid withdrawal symptoms. Further, we ran a pilot single-blind, randomized, controlled trial (34 heroin addicts) to evaluate the efficacy and safety of pregabalin in the treatment of opioid withdrawal syndrome. Pregabalin alone did not induce glutamate receptor neuroplasticity of dopamine neurons in the ventral tegmental area, but pre-treatment with pregabalin suppressed morphine-induced neuroplasticity, hyperlocomotion and morphine self-administration. Pregabalin administration after chronic morphine exposure failed to induce any rewarding effects. Instead, pregabalin suppressed withdrawal symptoms in both morphine-treated mice and opioid addicts and was well tolerated. Intriguingly, pregabalin administration after a low dose of morphine strongly facilitated ventral tegmental area neuroplasticity and led to increased conditioned place preference. Pregabalin appears to have the efficacy to counteract both reinforcing and withdrawal effects of opioids, but it also has a potentiating effect when given to mice with existing opioid levels.


Advanced Reinforcement Learning and Its Connections with Brain Neuroscience.
In recent years, brain science and neuroscience have greatly propelled the innovation of computer science. In particular, knowledge from the neurobiology and neuropsychology of the brain revolutionized the development of reinforcement learning (RL) by providing novel interpretable mechanisms of how the brain achieves intelligent and efficient decision making. Triggered by this, there has been a boom in research about advanced RL algorithms that are built upon the inspirations of brain neuroscience. In this work, to further strengthen the bidirectional link between the 2 communities and especially promote the research on modern RL technology, we provide a comprehensive survey of recent advances in the area of brain-inspired/related RL algorithms. We start with basis theories of RL, and present a concise introduction to brain neuroscience related to RL. Then, we classify these advanced RL methodologies into 3 categories according to different connections of the brain, i.e., micro-neural activity, macro-brain structure, and cognitive function. Each category is further surveyed by presenting several modern RL algorithms along with their mathematical models, correlations with the brain, and open issues. Finally, we introduce several important applications of RL algorithms, followed by the discussions of challenges and opportunities for future research.


The outcome of critically ill elderly patients with severe acute renal failure treated by continuous hemodiafiltration.
To study the outcome of critically ill elderly patients with severe acute renal failure managed by continuous hemodiafiltration. Prospective study. Intensive Care Unit of tertiary institution Seventy-two consecutive critically ill patients of 65 years or older admitted to the ICU with severe acute renal failure. Seventy similar control patients of age < 65 years. Treatment of all patients with continuous hemodiafiltration. Safety and effectiveness of therapy were assessed. Main outcome measures were duration of oliguria, of ICU stay, and hospital stay for survivors, and survival to ICU discharge and to hospital discharge. Mean APACHE II score on admission was 29.8 (95% confidence interval: 28.5 to 31.1) and mean organ failure score prior to initiation of continuous hemodiafiltration was 3.9 (95% confidence interval: 3.6 to 4.2). Sepsis was present in 51 cases (70.8%) and bacteremia or fungemia in 24 (33.3%). Fifty-three (73.6%) required mechanical ventilation for > 3 days. Vasopressor drugs were used in 65 (90.2%). Continuous hemodiafiltration controlled azotemia in all patients and was only associated with minor complications. Thirty-four patients (47.2%) survived to ICU discharge and 30 (41.6%) to hospital discharge. Among survivors, duration of oliguria was 11.6 days (95% confidence interval: 9.1 to 14.1), mean duration of ICU stay 8.6 days (95% confidence interval: 6.1 to 11.) and mean duration of hospital stay 33.1 days (95% confidence interval: 28.8 to 37.4). No statistically significant difference in survival was found when these patients were compared to a control group of similar but younger patients who also received ICU care and continuous hemodiafiltration for the treatment of severe acute renal failure. A greater than 40% survival was achieved in critically ill elderly patients with severe acute renal failure by the use of continuous hemodiafiltration. These patients had an in hospital survival comparable to that of younger patients. These findings support an aggressive renal replacement approach in such patients and suggest that continuous hemodiafiltration may be ideally suited to their management.


Inorganic Nanowires-Assembled Layered Paper as the Valve for Controlling Water Transportation.
Layered materials with open interlayer channels enable various applications such as tissue engineering, ionic and molecular sieving, and electrochemical devices. However, most reports focus on the two-dimensional nanosheets-assembled layered materials, whose interlayer spacing is limited at the nanometer scale. Herein, we demonstrate that one-dimensional inorganic nanowires are the ideal building blocks for the construction of layered materials with open interlayer channels as well, which has not aroused much attention before. It is found that the relatively long inorganic nanowires are capable of assembling into free-standing layered paper with open interlayer channels during the filtration process. The spacings of interlayer channels between adjacent layers are up to tens of micrometers, which are much larger than those of the two-dimensional nanosheets-assembled layered materials. But the closed interlayer channels are observed when the relatively short inorganic nanowires are used as building blocks. The mechanism based on the relationship between the structural variation and the nanowires used is proposed, including the surface charge amplified effect, surface charge superimposed effect, and pillarlike supporting effect. According to the proposed mechanism, we have successfully fabricated a series of layered paper sheets whose architectures (including interlayer channels of cross section and pores on the surface) show gradient changes. The as-prepared layered paper sheets are employed as the valves for controlling water transportation. Tunable water transportation is achieved by the synergistic effect between in-plane interlayer channels (horizontal transportation) from the open to the closed states, and through-layer pores (vertical transportation) without surface modification or intercalation of any guest species.


The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment.
Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in MEFV, which encodes a 781-amino acid protein denoted pyrin. We have previously shown that pyrin regulates caspase-1 activation and IL-1beta production through interaction of its N-terminal PYD motif with the ASC adapter protein, and also modulates IL-1beta production by interaction of its C-terminal B30.2 domain with the catalytic domains of caspase-1. We now asked whether pyrin might itself be a caspase-1 substrate, and found that pyrin is cleaved by caspase-1 at Asp330, a site remote from the B30.2 domain. Pyrin variants harboring FMF-associated B30.2 mutations were cleaved more efficiently than wild-type pyrin. The N-terminal cleaved fragment interacted with the p65 subunit of NF-kappaB and with IkappaB-alpha through its 15-aa bZIP basic domain and adjacent sequences, respectively, and translocated to the nucleus. The interaction of the N-terminal fragment with p65 enhanced entrance of p65 into the nucleus. The interaction of N-terminal pyrin with IkappaB-alpha induced calpain-mediated degradation of IkappaB-alpha, thus potentiating NF-kappaB activation. Absolute and relative quantities of cleaved pyrin and IkappaB-alpha degradation products were substantially increased in leukocytes from FMF patients compared with healthy controls. Our data support a new pyrin/caspase-1 pathway for NF-kappaB activation.


Impact of the COVID-19 Pandemic on the Wellness of Canadian Plastic Surgery Residents.
On top of preexisting burnout, depression, and anxiety among trainees, the COVID-19 pandemic has introduced novel stressors. The objectives of this study were to determine the effects of the COVID-19 pandemic on Canadian plastic surgery residents' practice, wellness, and overall training. Surveys for program directors and residents were created and disseminated to all English-speaking Canadian plastic surgery residency training programs. Survey results were pooled and presented as a percentage of responses for each question. Response rates were 50% (n = 5/10) and 25% (n = 19/77) for program directors and residents, respectively. All program directors believed that the pandemic has a negative effect on resident wellness, 80% (n = 4/5) of which believed that their residents were coping effectively. They rated program support for resident wellness as neutral or supportive. Most programs (80%; n = 4/5) introduced strategies to support resident well-being. Most trainees (84%; n = 16/19) reported the pandemic as having a negative effect on their well-being, with approximately 50% endorsing worse emotional, social, psychological, and physical wellness, as well as feelings of burnout. Some reported difficulties coping (21%; n = 4/19). Residents felt that their wellness was supported externally by their own resilience (89%; n = 17/19), family members (74%; n = 14/19), friends (74%; n = 14/19), their partner (68%; n = 13/19), or co-residents (53%; n = 10/19). Internal support by their program was rated as neutral or negative (63%; n = 12/19). Our findings of negative effects of the COVID-19 pandemic on the wellness of Canadian plastic surgery trainees are concerning. Programs must implement appropriate identification and support strategies to improve resident well-being.


Antibiotic failure in a renal transplant patient with Rhodococcus equi infection: an indication for surgical lobectomy.
Rhodococcus equi is an animal pathogen that causes infrequent but challenging infections in immunocompromised individuals, few of which have been described in solid organ transplant recipients. Common clinical presentations include indolent cough, fever, and dyspnea, with necrotizing pneumonia and cavitation. We report a case of a dense right upper lung pneumonia with resultant R. equi bacteremia in a renal transplant recipient. Our patient initially responded to antibiotic treatment with resolution of bacteremia and clinical recovery, followed by interval progression in her right upper lobe consolidation on follow-up computed tomography scans. She underwent lobectomy for definitive therapy with resolution of symptoms. Lobectomy can be utilized in isolated infection after antibiotic failure with excellent clinical outcomes.


Heritability of progeny size in a terrestrial isopod: transgenerational environmental effects on a life history trait.
Maternal effects, the environment that mothers provide to their offspring, their provision of nutrients and the environment that offspring of the same clutch share, have come to be recognized as an important influence on offspring fitness. In addition, in invertebrates, maternal effects and common environment may change according to a mother's diet. We tested for the changes in quantitative genetic parameters in a half-sib design where mothers were fed diets varying in nutrient content. Surprisingly, we found that not only maternal and common environmental variance changed with experimental diets but also there were significant changes in narrow-sense heritabilities, with corresponding h(2) values of 0.61 (high protein), 0.08 (high carbohydrate) and 0.001 (equal carbohydrate:protein). Our results show how an environmentally driven evolutionary process could occur in nature, since the response to selection could change dramatically according to the composition of the diet that females are ingesting.


Human lymphokine-activated killer cells develop syngeneic killing ability.
Lymphokine-activated killer (LAK)-cell therapy has emerged as a new strategy in designing protocols for the treatment of cancer. However, in its present clinical form, it has not fulfilled the early promise shown in murine models of human metastatic disease. In an attempt to gain understanding as to why this might be the case, we measured the ability of human LAK cells, generated in vitro for 4 days, to kill LAK cells from the same donor that had been exposed to IL-2 in vitro for 8 days, and vice versa. In eight separate experiments using different donors, 4-day ('early') LAK cells were able to kill syngeneic 8-day ('late') LAK cells, while late LAK cells were also able to kill early LAK cells. Strong killing was observed in both directions, which was almost total in one instance. In order to assess the development of this phenomenon, early LAK cells were tested for their ability to kill syngeneic LAK cells that were 1, 2, 3 or 4 days 'older' and the reciprocal experiment conducted using late LAK cells as effectors. The results illustrate a strong capacity for the development of syngeneic killing by human LAK cells. The possible implications of this phenomenon for the clinical administration of LAK cell/IL-2 therapy are discussed.


SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs.
Significance: Sulfur has a critical role in protein structure/function and redox status/signaling in all living organisms. Although hydrogen sulfide (H2S) and sulfane sulfur (SS) are now recognized as central players in physiology and pathophysiology, the full scope and depth of sulfur metabolome's impact on human health and healthy longevity has been vastly underestimated and is only starting to be grasped. Since many pathological conditions have been related to abnormally low levels of H2S/SS in blood and/or tissues, and are amenable to treatment by H2S supplementation, development of safe and efficacious H2S donors deserves to be undertaken with a sense of urgency; these prodrugs also hold the promise of becoming widely used for disease prevention and as antiaging agents. Recent Advances: Supramolecular tuning of the properties of well-known molecules comprising chains of sulfur atoms (diallyl trisulfide [DATS], S8) was shown to lead to improved donors such as DATS-loaded polymeric nanoparticles and SG1002. Encouraging results in animal models have been obtained with SG1002 in heart failure, atherosclerosis, ischemic damage, and Duchenne muscular dystrophy; with TC-2153 in Alzheimer's disease, schizophrenia, age-related memory decline, fragile X syndrome, and cocaine addiction; and with DATS in brain, colon, gastric, and breast cancer. Critical Issues: Mode-of-action studies on allyl polysulfides, benzyl polysulfides, ajoene, and 12 ring-substituted organic disulfides and thiosulfonates led several groups of researchers to conclude that the anticancer effect of these compounds is not mediated by H2S and is only modulated by reactive oxygen species, and that their central model of action is selective protein S-thiolation. Future Directions: SG1002 is likely to emerge as the H2S donor of choice for acquiring knowledge on this gasotransmitter's effects in animal models, on account of its unique ability to efficiently generate H2S without byproducts and in a slow and sustained mode that is dose independent and enzyme independent. Efficient tuning of H2S donation characteristics of DATS, dibenzyl trisulfide, and other hydrophobic H2S prodrugs for both oral and parenteral administration will be achieved not only by conventional structural modification of a lead molecule but also through the new "supramolecular tuning" paradigm.


Surgical and histopathological effects of topical Ankaferd® hemostat on major arterial vessel injury related to elevated intra-arterial blood pressure.
The aim of this study was to assess the surgical and histopathological hemostatic effects of topical Ankaferd blood stopper (ABS) on major arterial vessel injury related to elevated intra-arterial blood pressure in an experimental rabbit model. The study included 14 New Zealand rabbits. ABS was used to treat femoral artery puncture on 1 side in each animal and the other untreated side served as the control. Likewise, for abdominal aortic puncture, only 50% of the aortic injuries received topical liquid ABS and the others did not (control). The experiment was performed under conditions of normal arterial blood pressure and was repeated with a 50% increase in blood pressure. Histopathological analysis was performed in all of the studied animals. Mean bleeding time in the control femoral arteries was 105.0±18.3 s, versus 51.4±9.8 s (p<0.05) in those treated with ABS. Mean blood loss from the punctured control femoral arteries was 5.0±1.5 mg and 1.6±0.4 mg from those treated with ABS (p<0.05). Histopathological examination of the damaged arterial structures showed that ABS induced red blood cell aggregates. ABS administered to experimental major arterial vessel injury reduced both bleeding time and blood loss under conditions of normal and elevated intra-arterial blood pressure. ABS-induced erythroid aggregation was prominent at the vascular tissue level. These findings will inform the design of future experimental and clinical studies on the anti-bleeding and vascular repairing effects of the novel hemostatic agent ABS.


[Study on the risk factors related vertical transmission of HBV positive couples to their infant].
To explore the risk factors and the rate of HBV vertical transmission from HBsAg-positive couple to their infant. 46 families who had antenatal examination at Fujian Provincial Maternal and Child Health Hospital during August 2010 and November 2011 were chosen as research object. Cord blood was sampled after delivery for HBVM and HBV-DNA quantification. Those with HBV-DNA load ≥ 5 × 10(2) copies/ml were involved in the case group while those having < 5 × 10(2) copies/ml were chosen as controls. The average positive rate of neonatal cord blood HBV-DNA was 45.7% (21/46), while the positive rates of cord blood HBsAg and HBeAg were 34.8% (16/46) and 23.9% (11/46) respectively. The positive rates of maternal serum HBV-DNA and paternal serum HBV-DNA were 52.2% (24/46) and 69.6% (32/46) respectively, with the positive rate of couple serum HBeAg as 39.1% (18/46) and 32.6% (15/46) respectively. Results from univariate analysis showed that hepatitis B surface markers, serum HBeAg-positive, serum HBV-DNA positive, and serum HBV-DNA load of the couples were risk factors to the HBV vertical transmission (χ(2) = 8.731, 8.414, 8.932, 9.663, 10.823, 3.962, 13.638, 36.501; P < 0.05). Data from the multivariate analysis showed that maternal serum HBV-DNA positive and paternal serum HBV-DNA load were risk factors to the HBV vertical transmission[OR = 17.6 (1.3 - 238.4) ; OR = 3.5 (1.6-7.6)]. Serum HBV-DNA loads of the couples were positively correlated with the cord blood HBV-DNA load, while the load levels of the couple's serum HBV-DNA were higher than cord blood HBV-DNA. There appeared dose-response relationship between couple's serum HBV-DNA load level and the cord blood HBV-DNA load level. from the analysis of ROC curve showed that both maternal serum HBV-DNA load level (10(3) copies/ml) and paternal serum HBV-DNA load level (10(4) copies/ml) were demarcation points to better forecast the occurrence of vertical transmission of HBV, because there showed higher sensitivity and specificity for the forecasting process. Neonatal outcomes showed no significant difference between the case group and the control group. The negative conversion rate became 15.0% (3/20) when the HBV-DNA positive infants were followed up for 7 months. Both maternal serum HBV-DNA positive and paternal serum HBV-DNA load were risk factors of HBV vertical transmission. When the maternal serum HBV-DNA load appeared > 10(3) copies/ml and paternal serum HBV-DNA load > 10(4) copies/ml, the rate of HBV vertical transmission would increase.


Diffusion-weighted MRI of spinal cord infarction--high resolution imaging and time course of diffusion abnormality.
Infarction is a rare cause of spinal cord dysfunction. Whereas diffusion-weighted (DW) MRI has been established as a highly sensitive technique for assessing acute cerebral ischemia, its role in spinal cord infarction remains to be determined. The purpose of this study is to present the signal characteristics of acute spinal cord ischemia using DWMRI within the first two days and after one week. MRI including DW imaging (DWI) was performed in three patients with acute spinal cord dysfunction 8, 12 and 30 hours after the onset of symptoms and repeated after one week in two patients. Two initial scans included EPI DW sequences in transverse and sagittal orientation. The remaining examinations were performed with an optimised high-spatial resolution DWI sequence in the transverse plane. The diagnosis of spinal cord ischemia was established by imaging, clinical history and CSF analysis. T2 signal abnormality and restricted diffusion was demonstrated in all initial examinations. Transverse DW sequences had the highest sensitivity. The spinal infarctions were mainly located in the centre of the spinal cord and the grey matter. Contrast enhancement was absent. After one week, the restricted diffusion had normalised (pseudo normalisation) whereas the T2 signal changes had become more prominent. Restricted diffusion in the course of spinal cord ischemic infarction can be demonstrated using DW-MRI. Whereas a diffusion abnormality can be found after few hours, it does not last for longer than one week. At this time, the establishment of the diagnosis has to rely mainly on T2-weighted images with additional post contrast T1-weighted images being useful.


Combining Clinicopathological Parameters and Molecular Indicators to Predict Lymph Node Metastasis in Endometrioid Type Endometrial Adenocarcinoma.
Lymph node metastasis (LNM) is a critical unfavorable prognostic factor in endometrial cancer (EC). At present, models involving molecular indicators that accurately predict LNM are still uncommon. We addressed this gap by developing nomograms to individualize the risk of LNM in EC and to identify a low-risk group for LNM. In all, 776 patients who underwent comprehensive surgical staging with pelvic lymphadenectomy at the First Affiliated Hospital of Chongqing Medical University were divided into a training cohort (used for building the model) and a validation cohort (used for validating the model) according to a predefined ratio of 7:3. Logistics regression analysis was used in the training cohort to screen out predictors related to LNM, after which a nomogram was developed to predict LNM in patients with EC. A calibration curve and consistency index (C-index) were used to estimate the performance of the model. A receiver operating characteristic (ROC) curve and Youden index were used to determine the optimal threshold of the risk probability of LNM predicted by the model proposed in this study. Then, the prediction performance of different models and their discrimination abilities for identifying low-risk patients were compared. LNM occurred in 87 and 42 patients in the training and validation cohorts, respectively. Multivariate logistic regression analysis showed that histological grade (P=0.022), myometrial invasion (P=0.002), lymphovascular space invasion (LVSI) (P=0.001), serum CA125 (P=0.008), Ki67 (P=0.012), estrogen receptor (ER) (0.009), and P53 (P=0.003) were associated with LNM; a nomogram was then successfully established on this basis. The internal and external calibration curves showed that the model fits well, and the C-index showed that the prediction accuracy of the model proposed in this study was better than that of the other models (the C-index of the training and validation cohorts was 0.90 and 0.91, respectively). The optimal threshold of the risk probability of LNM predicted by the model was 0.18. Based on this threshold, the model showed good discrimination for identifying low-risk patients. Combining molecular indicators based on classical clinical parameters can predict LNM of patients with EC more accurately. The nomogram proposed in this study showed good discrimination for identifying low-risk patients with LNM.


Binding of the sea anemone polypeptide BDS II to the voltage-gated sodium channel.
BDS II, a 43-residue polypeptide from the sea anemone Anemonia sulcata, is reported to have both antihypertensive and antiviral activity. This polypeptide possesses a number of sequence and structural similarities to a class of cardiotonic proteins which bind to receptor site 3 of the voltage-gated sodium channel. In contrast to these cardiostimulant proteins, which produce positive inotropic effects at concentrations of 2-15 nM, BDS II produced a weak negative inotropic effect upon isolated guinea-pig atria, with doses of 90 and 180 nM depressing contractile strength by 15 and 28%, respectively. BDS II also competed with a 125-iodine labelled derivative of AP-A (a representative of the cardiostimulant proteins) bound to sodium channels in rat brain synaptosomes. The IC50 for BDS II versus AP-A was 5.2 microM. BDS II may therefore be considered an antagonist for receptor site 3 of the voltage-gated sodium channel. Structural differences between BDS II and the agonist AP-A which may give rise to their different effects on the sodium channel are considered.


Psychrometric limits and critical evaporative coefficients for unacclimated men and women.
Critical environmental limits, defined as those above which heat balance cannot be maintained for a given metabolic heat production, have not been determined for unacclimated subjects. To characterize critical environmental limits and to derive evaporative heat exchange coefficients (K(e)') for unacclimated young men (n = 11) and women (n = 10), subjects of average aerobic fitness walked at 30% maximal aerobic capacity in an environmental chamber. Critical environmental conditions were defined as the psychrometric loci of dry-bulb temperature and water vapor pressure at which core (esophageal) temperature was forced out of equilibrium (heat gain exceeded heat loss). Compared with the men in our study, the women had significantly higher critical environmental limits (P < 0.001) in warm (34-38 degrees C), humid (>60%) environments, a function of their lower absolute metabolic heat production at the fixed relative exercise intensity. Isotherms constructed from biophysical models closely fit the data in this range of environments but underestimated empirically determined critical limits in hotter, drier environments. Sex-specific values of K(e)' were derived by partial calorimetry in the critical water vapor pressure environments, in which full skin wettedness occurred. There were no sex differences for K(e)' (men = 17.4, 15.5, and 14.2 W. m(-2). Torr(-1) and women = 16.8, 15.5, and 14.2 W. m(-2). Torr(-1) at 34, 36, and 38 degrees C, respectively). These K(e)' values were lower than those previously published for fully heat-acclimated men (18.4 W. m(-2). Torr(-1) at 36 degrees C) and women (17.7 W. m(-2). Torr(-1) at 36 degrees C and 15.5 W. m(-2). Torr(-1) at 38 degrees C) and may be used to model heat balance responses for unacclimated men and women working in hot environments.