Emergency department crowding is associated with poor care for patients with severe pain.
We study the impact of emergency department (ED) crowding on delays in treatment and nontreatment for patients with severe pain. We performed a retrospective cohort study of all patients presenting with severe pain to an inner-city, teaching ED during 17 months. Poor care was defined by 3 outcomes: not receiving treatment with pain medication while in the ED, a delay (>1 hour) from triage to first pain medication, and a delay (>1 hour) from room placement to first pain medication. Three validated crowding measures were assigned to each patient at triage. Logistic regression was used to test the association between crowding and outcomes. In 13,758 patients with severe pain, the mean age was 39 years (SD 16 years), 73% were black, and 64% were female patients. Half (49%) of the patients received pain medication. Of those treated, 3,965 (59%) experienced delays in treatment from triage and 1,319 (20%) experienced delays from time of room placement. After controlling for factors associated with the ED treatment of pain (race, sex, severity, and older age), nontreatment was independently associated with waiting room number (odds ratio [OR] 1.03 for each additional waiting patient; 95% confidence interval [CI] 1.02 to 1.03) and occupancy rate (OR 1.01 for each 10% increase in occupancy; 95% CI 0.99 to 1.04). Increasing waiting room number and occupancy rate also independently predicted delays in pain medication from triage (OR 1.05 for each waiting patient, 95% CI 1.04 to 1.06; OR 1.18 for each 10% increase in occupancy; 95% CI 1.15 to 1.21) and delay in pain medication from room placement (OR 1.02 for each waiting patient, 95% CI 1.01 to 1.03; OR 1.06 for each 10% increase in occupancy, 95% CI 1.04 to 1.08). ED crowding is associated with poor quality of care in patients with severe pain, with respect to total lack of treatment and delay until treatment.


Hepatitis B surface antigen loss in chronic hepatitis B virus and HIV-1 Co-Infections individuals in Botswana.
We sought to determine hepatitis B surface antigen (HBsAg) loss and its predictors among people with chronic hepatitis B (CHB) infections and HIV (PWH) in Botswana. Archived plasma samples from a cohort of PWH in Botswana (2013-2018) with 3 yearly time-points were used. Samples were screened for HBsAg, immunoglobulin M HBV core antibodies (anti-HBc IgM) and HBV e-antigen (HBeAg) at all time points. HBV deoxyribonucleic acid (DNA) quantification was done at baseline. The Wilcoxon rank-sum was used to compare continuous variables while the chi-squared test and Fishers exact test were used for categorical data where appropriate. Logistic regression was used to assess predictors of seroclearance. Of 141 participants with HBsAg positive serology (HBsAg+) at baseline, 92.2% (131/141) [95% CI: 87.4-96.1] were persistently HBsAg+ at year 1. We report a HBsAg loss of 7.1% (10/141) [95% CI: 3.9-12.6] among participants with negative HBeAg and negative IgM serologies. HBsAg loss was 6.3% (7/111) among ART-experienced participants and 10.7% (3/28) [95% CI:0.4-5.0] in ART-naïve participants. Most participants who had positive anti-HBc IgM serology and did not lose HBsAg were on either 3TC-based therapy or non-TDF-based therapy, except for one participant. The participants also had varying HBeAg status. HBsAg loss was independent of HIV viral load, CD4 count, age and sex. We report a HBsAg loss of 6.3% over a 3 year period among ART-experienced CHB participants. Future studies that focus on HBsAg loss in mono-infected patients and the possible correlation between HBeAg status and HBsAg loss are warranted.


Effect of episodic hypoxia on upper airway mechanics in humans during NREM sleep.
We hypothesized that long-term facilitation (LTF) is due to decreased upper airway resistance (Rua). We studied 11 normal subjects during stable non-rapid eye movement sleep. We induced brief isocapnic hypoxia (inspired O(2) fraction = 8%) (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 20 min of recovery (R(20)) for ventilation, timing, and Rua. In addition, nine subjects were studied in a sham study with no hypoxic exposure. During the episodic hypoxia study, inspiratory minute ventilation (VI) increased from 7.1 +/- 1.8 l/min during the control period to 8.3 +/- 1.8 l/min at R(20) (117% of control; P < 0.05). Conversely, there was no change in diaphragmatic electromyogram (EMG(dia)) between control (16.1 +/- 6.9 arbitrary units) and R(20) (15.3 +/- 4.9 arbitrary units) (95% of control; P > 0.05). In contrast, increased VI was associated with decreased Rua from 10.7 +/- 7.5 cmH(2)O. l(-1). s during control to 8.2 +/- 4.4 cmH(2)O. l(-1). s at R(20) (77% of control; P < 0.05). No change was noted in VI, Rua, or EMG(dia) during the recovery period relative to control during the sham study. We conclude the following: 1) increased VI in the recovery period is indicative of LTF, 2) the lack of increased EMG(dia) suggests lack of LTF to the diaphragm, 3) reduced Rua suggests LTF of upper airway dilators, and 4) increased VI in the recovery period is due to "unloading" of the upper airway by LTF of upper airway dilators.


Regulation of the glial glutamate transporter GLT-1 by glutamate and delta-opioid receptor stimulation.
The excitatory effect of presynaptically released glutamate is tightly regulated and terminated by high affinity sodium-dependent glutamate transporters. The regulation of the glial glutamate transporter GLT-1 is potentially important in synaptic modulation. Using astroglial cultures prepared from the rat cerebral cortex, we found that the delta-opioid receptor agonist [D-pen2,D-pen5]-enkephalin decreases and glutamate increases the expression of the GLT-1 transporter mRNA. Corresponding changes in the uptake kinetics were found after incubation for 48 h with the respective agonists when glial glutamate uptake was measured in primary astroglial cultures. The data suggest that long-term receptor activation induces alterations in glial glutamate uptake properties.


Sequence requirements for stable binding and function of Rep68 on the adeno-associated virus type 2 inverted terminal repeats.
Replication of the palindromic inverted terminal repeats (ITRs) of adeno-associated virus type 2 requires several functions of the viral nonstructural Rep proteins. These include binding to the ITR, nicking of the double-stranded replication intermediate at the terminal resolution site (trs), and then strand displacement and synthesis from the nick. This report demonstrates the ability of both recombinant fusion maltose-binding protein (MBP)-Rep68 delta produced in Escherichia coli and wild-type (wt) Rep68 to bind to a linear truncated form of the ITR, delta 57 ITR, with similar affinity as to the wt hairpin ITR. A dissociation constant for MBP-Rep68 delta of approximately 8 x 10(-10) M was determined for the wt ITR and delta 57 ITR probes. Truncation of delta 57 ITR to generate delta 28 ITR, which retains the GCTC repeat motif but not the trs, bound at least 10 times less efficiently than delta 57 ITR. Extension of delta 28 ITR with nonspecific sequence restored the ability of MBP-Rep68 delta to bind to delta 28 ITR. Thus, high-affinity binding would appear to require stabilization by flanking sequence as well as the intact GCTC repeat motif. Cleavage of the delta 57 ITR probe with DdeI, which truncates the flanking sequence and was previously shown to inhibit binding by Rep68, also inhibited the binding of MBP-Rep68 delta. The requirements for stable binding were further defined with a series of oligonucleotide probes which spanned the region protected by MBP-Rep78 in DNase I footprinting. The binding activity of either MBP-Rep68 delta or wt Rep68 to hairpin ITR or delta 57 ITR was indistinguishable. However, the binding activity of MBP-Rep68 delta to DNA does not appear to correlate with trs endonuclease activity. The nicking and covalent linkage of MBP-Rep68 delta to the nonhairpin delta 57 ITR was approximately 100-fold less efficient than its linkage to a hairpin-containing ITR. Therefore, although the hairpin portion of the ITR does not appear to play a role in recognition and stabilization of MBP-Rep68 delta binding, its presence does affect the trs cleavage activity of the protein.


Structure-Based Discovery of a Series of 5H-Pyrrolo[2,3-b]pyrazine FGFR Kinase Inhibitors.
Fibroblast growth factor receptors (FGFRs), a subfamily of receptor tyrosine kinases, are aberrant in various cancer types, and considered to be promising targets for cancer therapy. We started with a weak-active compound that was identified from our internal hepatocyte growth factor receptor (also called c-Met) inhibitor project, and optimized it with the guidance of a co-crystal structure of compound 8 with FGFR1. Through rational design, synthesis, and the biological evaluation of a series of 5H-pyrrolo[2,3-b]pyrazine derivatives, we discovered several potent FGFR kinase inhibitors. Among them, compound 13 displayed high selectivity and favorable metabolic properties, demonstrating a promising lead for further development.


Oral sustained delivery of theophylline and cimetidine from in situ gelling pectin formulations in rabbits.
The aim of this study was to evaluate the potential of an in situ gelling pectin formulation as a vehicle for the oral sustained delivery of theophylline and cimetidine. In vitro studies demonstrated diffusion-controlled release of theophylline from 1, 1.5, and 2% w/v pectin gels. Release of this drug from 1.5% w/v pectin gels formed in situ in rabbit stomach was sustained over a period of 12 hours giving a theophylline bioavailability some seven fold higher than when administered from a commercial syrup. In contrast, interactions between cimetidine and pectin led to weak gelation of the pectin sols that prevented any meaningful determination of in vitro release characteristics. Similarly, in vivo release profiles from pectin formulations containing cimetidine were similar to that from a solution of this drug in buffer, indicative of weak gelation. Examination of the content of the rabbit stomach 5 hours after administration of 1.5% w/v pectin sols containing drug confirmed gel formation, but gels containing cimetidine were noticeably softer than those containing theophylline.


Modulation of the Early Host Response to Electrospun Polylactic Acid Matrices by Mesenchymal Stem Cells from the Amniotic Fluid.
The reconstruction of congenital diaphragmatic hernia or other congenital soft tissue defects often requires implants. These can be either degradable or permanent, each having their advantages. Whatever type is being used, the host response induced by implants plays a crucial role to determine the outcome. Macrophages are pivotal during implant remodeling; they are plastic and acquire in response to environmental stimuli either an inflammatory status and mediate subsequent fibrosis or a regulatory status and facilitate functional remodeling. Matrices engineered with mesenchymal stem cells (MSCs) have the capacity to modulate the host immune reaction. MSCs are believed to promote constructive remodeling of the implant through a regulatory macrophage response among others. Herein, we evaluate this potential of MSC derived from the amniotic fluid (AF-MSC), an interesting MSC type for neonatal reconstruction, on electrospun polylactic acid (PLA) scaffolds. We seeded AF-MSC at a density of 1.105/cm2 on electrospun PLA matrices and determined cell viability. In vivo, we used cell-seeded or cell-free PLA matrices for subcutaneous implantation in immune competent rats. The host immune response was evaluated by histomorphometry at 14 days postoperatively. The PLA matrix supported adherence and proliferation of AF-MSC. Fourteen days after implantation, PLA matrices were well penetrated by inflammatory cells, new blood vessels, and collagen fibers. AF-MSC-seeded scaffolds were associated with a similar response yet with a decreased number of eosinophils, increased matrix degradation and collagen fiber deposition compared with controls. The amount of total macrophages and of M2-subtype was similar for all animals. Electrospun PLA matrices are a suitable substrate for short-term culture of AF-MSC. In rats, addition of AF-MSC to PLA matrices modulates the host response after subcutaneous implantation, yet without a difference in macrophage profile compared with control.


Functionally disconnected: A look at how study design influences neurofeedback data and mechanisms in attention-deficit/hyperactivity disorder.
Neurofeedback (NF) is a form of behavioral therapy used to treat e.g. attention-deficit/hyperactivity disorder (ADHD). Briefly, subjects are fed-back a putatively dysfunctional parameter of their brain activity in real time and must learn to control it in a suggested direction. NF protocols for ADHD have been used in practice for decades, though no clear standards on NF design have been implemented. Furthermore, studies often present only data from the general outcome of the NF treatment and do not look at how exactly the NF paradigm affects brain functionality, or what exactly the NF is training. The current study is two-fold: firstly, we look at how the functional connectivity (FC) patterns within key networks associated with ADHD differ between rests, feedback trials, success and failure in a complete functional near-infrared spectroscopy-based NF experiment on adults with ADHD. Secondly, due to methodological concerns discovered during the analysis of our data, we address important considerations in the design of NF that are often ignored in protocols being used widely in therapy and research today. In particular, we examine the common average reference and its impact on network activity as well as the importance of balancing the randomization in a design. Finally, we discuss how these methodological considerations may have influenced our FC results.


[The university pharmacy and the university pharmacist in history].
The major purpose of the research is to show the influence of university pharmacy and university pharmacist on the development of pharmaceutical science. The lectures in materia medica were frequent realized in university pharmacy since middle age. In the 18th century the university pharmacy was in some cases the precursor to the institute of pharmaceutical chemistry. In the paper also a summary is given of the importance of extensive activity of the university pharmacists J.D. Leers, G.L.C. Rousseau, J.R. Spielmann, F.C. Lieblein, A.F. Duflos, E.F. Jahns, W. Mettenheimer, C. Brunnengräber, C.A. Laubinger, J. Stamm, O.H. Gerke and E. Weber.


Grey matter atrophy in prodromal stage of dementia with Lewy bodies and Alzheimer's disease.
Little is known about the patterns of brain atrophy in prodromal dementia with Lewy bodies (pro-DLB). In this study, we used SPM8 with diffeomorphic anatomical registration through exponentiated lie algebra to measure grey matter (GM) volume and investigate patterns of GM atrophy in pro-DLB (n = 28) and prodromal Alzheimer's disease (pro-AD) (n = 27) and compared and contrasted them with those in elderly control subjects (n = 33) (P ≤ 0.05 corrected for family-wise error). Patients with pro-DLB showed diminished GM volumes of bilateral insulae and right anterior cingulate cortex compared with control subjects. Comparison of GM volume between patients with pro-AD and control subjects showed a more extensive pattern, with volume reductions in temporal (hippocampi and superior and middle gyri), parietal and frontal structures in the former. Direct comparison of prodromal groups suggested that more atrophy was evident in the parietal lobes of patients with pro-AD than patients with pro-DLB. In patients with pro-DLB, we found that visual hallucinations were associated with relative atrophy of the left cuneus. Atrophy in pro-DLB involves the insulae and anterior cingulate cortex, regions rich in von Economo neurons, which we speculate may contribute to the early clinical phenotype of pro-DLB.


Host genetic factors associated with symptomatic primary HIV infection and disease progression among Argentinean seroconverters.
Variants in HIV-coreceptor C-C chemokine receptor type 5 (CCR5) and Human leukocyte antigen (HLA) genes are the most important host genetic factors associated with HIV infection and disease progression. Our aim was to analyze the association of these genetic factors in the presence of clinical symptoms during Primary HIV Infection (PHI) and disease progression within the first year. Seventy subjects diagnosed during PHI were studied (55 symptomatic and 15 asymptomatic). Viral load (VL) and CD4 T-cell count were evaluated. HIV progression was defined by presence of B or C events and/or CD4 T-cell counts <350 cell/mm3. CCR5 haplotypes were characterized by polymerase chain reaction and SDM-PCR-RFLP. HLA-I characterization was performed by Sequencing. Symptoms during PHI were significantly associated with lower frequency of CCR5-CF1 (1.8% vs. 26.7%, p = 0.006). Rapid progression was significantly associated with higher frequency of CCR5-CF2 (16.7% vs. 0%, p = 0.024) and HLA-A*11 (16.7% vs. 1.2%, p = 0.003) and lower frequency of HLA-C*3 (2.8% vs. 17.5%, p = 0.035). Higher baseline VL was significantly associated with presence of HLA-A*11, HLA-A*24, and absence of HLA-A*31 and HLA-B*57. Higher 6-month VL was significantly associated with presence of CCR5-HHE, HLA-A*24, HLA-B*53, and absence of HLA-A*31 and CCR5-CF1. Lower baseline CD4 T-cell count was significantly associated with presence of HLA-A*24/*33, HLA-B*53, CCR5-CF2 and absence of HLA-A*01/*23 and CCR5-HHA. Lower 6-month CD4 T-cell count was associated with presence of HLA-A*24 and HLA-B*53, and absence of HLA-A*01 and HLA-B*07/*39. Moreover, lower 12-month CD4 T-cell count was significantly associated with presence of HLA-A*33, HLA-B*14, HLA-C*08, CCR5-CF2, and absence of HLA-B*07 and HLA-C*07. Several host factors were significantly associated with disease progression in PHI subjects. Most results agree with previous studies performed in other groups. However, some genetic factor associations are being described for the first time, highlighting the importance of genetic studies at a local level.


Structure characterization of a novel polysaccharide from Dictyophora indusiata and its macrophage immunomodulatory activities.
A novel polysaccharide, here named DP1, was isolated from the fruiting body of Dictyophora indusiata using a water extraction method. Structure characterization revealed that DP1 had an average molecular weight of 1132 kDa and consisted of glucose (56.2%), galactose (14.1%), and mannose (29.7%). The main linkage type of DP1 were proven to be (1 → 3)-linked α-l-Man, (1 → 2,6)-linked α-d-Glc, (1 → 6)-linked β-d-Glc, (1 → 6)-linked β-d-Gal, and (1 → 6)-linked β-d-Man by periodate oxidation-Smith degradation and nuclear magnetic resonance analysis. The immunostimulating assay indicated that DP1 could significantly promote macrophage NO, TNF-α, and IL-6 secretion in murine RAW 264.7 cells involving complement receptor 3 (CR3). The immune activities of DP1 were quite stable under thermal processing (100, 121, and 145 °C). Besides, DP1 retained stability after acidic/alkline treatment (pH 4.0-10.0), which enabled it to be an ideal complementary medicine or functional food for therapeutics of hypoimmunity and immunodeficiency diseases.


Sage, Rosemary, and Bay Laurel Hydrodistillation By-Products as a Source of Bioactive Compounds.
Essential oils from Mediterranean wild plants are widely used, but the hydrodistillation residues produced in parallel with these essential oils are significantly understudied and underexploited. Since there are only fragmentary data in the literature, we have, for the first time, systematically analyzed the chemical composition of the by-products obtained after hydrodistillation of sage, bay laurel, and rosemary leaves, i.e., hydrolates, water residues, and solid residues. The chemical composition of the hydrolates changed compared to their respective essential oils towards the dominance of more hydrophilic, oxygenated compounds, such as camphor in sage, 1,8-cineole in bay laurel, and berbenone in rosemary. However, some compounds, mostly sesquiterpenes, which were present in considerable amounts in essential oils, were absent or only present in very small amounts in the hydrolates. Furthermore, both the water and the solid residues were rich in polyphenols, such as procyanidins in bay laurel and rosmarinic acid in rosemary and sage. In conclusion, we demonstrate the valuable chemical composition of sage, rosemary, and bay laurel hydrodistillation by-products and discuss a wide range of their possible applications.


Synthesis, Antifungal Ergosterol Inhibition, Antibiofilm Activities, and Molecular Docking on β-Tubulin and Sterol 14-Alpha Demethylase along with DFT-Based Quantum Mechanical Calculation of Pyrazole Containing Fused Pyridine-Pyrimidine Derivatives.
Multidrug-resistant fungal infections have become much more common in recent years, especially in immune-compromised patients. Therefore, researchers and pharmaceutical professionals have focused on the development of novel antifungal agents that can tackle the problem of resistance. In continuation to this, a novel series of pyrazole-bearing pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives (4a-4o) have been developed. These compounds have been screened against Candida albicans, Aspergillus niger, and Aspergillus clavatus. The synthesized compounds were characterized by well-known spectroscopic techniques, i.e., IR, 1H NMR, 13C NMR, and mass spectrometry. In vitro antifungal results revealed that compound 4n showed activity against C. albicans having MIC value of 200 μg/mL. To know the plausible mode of action, the active derivatives were screened for anti-biofilm and ergosterol biosynthesis inhibition activities. The compounds 4h, 4j, 4k, and 4n showed greater ergosterol biosynthesis inhibition than the control DMSO. To comprehend how molecules interact with the receptor, studies of molecular docking of 4k and 4n have been performed on the homology-modeled protein of β-tubulin. The molecular docking revealed that the active compounds 4h, 4j, 4k, 4l, and 4n interacting with the active site amino acid of sterol 14-alpha demethylase (PDB ID: 5v5z) indicate one of the possible modes of action of ergosterol inhibition activity. The synthesized compounds 4c, 4e, 4h, 4i, 4j, 4k, 4l, and 4n inhibited biofilm formation and possessed the potential for anti-biofilm activity. DFT-based quantum mechanical calculations were carried out to optimize, predict, and compare the vibration modes of the molecule 4a.


Quantitative depth profile analysis of micrometer-thick multilayered thin coatings using step-scan FT-IR photoacoustic spectroscopy.
This paper demonstrates the results of the comparison of step-scan FT-IR photoacoustic spectroscopy with other established spectroscopic and microscopic techniques in the quantitative depth profile determination of micrometer- and submicrometer-thick multilayered thin coatings. The power of the phase rotation and phase spectrum analytical methods to clearly distinguish the infrared signature of submicrometer-thick coatings is demonstrated. The thickness determined by the step-scan FT-IR photoacoustic method is in very reasonable agreement with optical microtomy/microscopy measurements performed at-line during the coating process. The former technique described in detailed here offers substantial benefits in terms of measurement time and operator dependency, while not sacrificing the accuracy of the measurement. The problem of saturation and its effect on "real-life" samples is also discussed.


[Nonspecific bronchial reactivity].
Nonspecific bronchial reactivity is defined as the ability of bronchial smooth muscles to contract in response to non-allergenic (nonspecific) stimuli. Recent techniques for its measurement in different experimental and clinical situations have opened up new avenues in the understanding of asthma, airway infection, cough, and effects of pollution. The most recent data suggest that airway inflammation is the central mechanism of bronchial hyperreactivity, but the cells and mediators involved remain to be discovered. Bronchial reactivity as a test for clinical purposes needs standardization, careful establishment of normal values and assessment of validity in terms of the decision-making process.


Neutral community model explains the bacterial community assembly in freshwater lakes.
Over the past decade, neutral theory has gained attention and recognition for its capacity to explain bacterial community structure (BCS) in addition to deterministic processes. However, no clear consensus has been drawn so far on their relative importance. In a metacommunity analysis, we explored at the regional and local scale the effects of these processes on the bacterial community assembly within the water column of 49 freshwater lakes. The BCS was assessed using terminal restriction fragment length polymorphism (T-RFLP) of the 16S rRNA genes. At the regional scales, results indicated that the neutral community model well predicted the spatial community structure (R(2) mean = 76%) compared with the deterministic factors - which explained only a small fraction of the BCS total variance (less than 14%). This suggests that the bacterial compartment was notably driven by stochastic processes, through loss and gain of taxa. At the local scale, the bacterial community appeared to be spatially structured by stochastic processes (R(2) mean = 65%) and temporally governed by the water temperature, a deterministic factor, even if some bacterial taxa were driven by neutral dynamics. Therefore, at both regional and local scales the neutral community model appeared to be relevant in explaining the bacterial assemblage structure.


Submandibular duct sialolithiasis : an unusual presentation.
Multiple calculi in a submandibular gland duct is an uncommon occurrence. One such case occurring in a young boy of 25 years is reported here where thirteen very small stones of 1-3 mm of maximum diameter were lined up in the Wharton's duct in such a way that they were difficult to appreciate on inspection and palpation. Successful exploration was done in two steps.


The osseointegration properties of titanium implants with hydroxyapatite submicron-scale features in the rabbit tibia.
The objective of this study was to biomechanically and histologically assess the stability and integration of titanium implants that include hydroxyapatite based submicron-scale features. Thirty-four 3.4 mm × 6.5 mm implants, equally split between test (grit blasted, etched, and submicron scale deposition) and control (grit blasted and etched) groups, were placed in the tibiae of New Zealand White rabbits. At 3-weeks follow-up, the group with the submicron deposition showed significantly improved bone response compared with the control group. The test group required higher removal torque values, with its post-torque histology demonstrating both enhanced bone formation and an intact interface indicative of a robust bone-to-implant bond.


Regulation of plasma agouti-related protein and its relationship with hunger in lean and obese men.
Agouti-related protein (AgRP) is an orexigenic (appetite stimulating) neuropeptide suggested to exert tonic control over long-term energy balance. While some have speculated AgRP is not involved in the episodic (i.e. meal to meal energy intake) control, acute decreases in plasma agouti-related protein (AgRP) following a meal have been observed in humans in a role consistent with episodic control for AgRP. Whether changes in plasma AgRP are associated with episodic, and/or tonic changes in appetite has yet to be directly examined. The present study examined the relationship between agouti-related protein (AgRP), leptin and the regulation of appetite following a 48-h fast and an acute meal challenge. Blood samples were obtained from young lean and obese men before and after a 48 h fast (lean n = 10; obese n = 7). Fasting resulted in an increase in AgRP and a decrease in leptin with these changes being greater in lean than obese. In addition, blood samples were obtained from lean men before and 1, 2, 3 and 4 h after a meal (n = 8). Following a meal, AgRP was reduced from 2 to 4 h, a change that was dissociated from both leptin and subjective measures of hunger and satiety. These results demonstrate that AgRP is not associated with changes in hunger or satiety, and can change without corresponding changes in leptin. This suggests that AgRP may not be involved in the episodic control of appetite and the release of AgRP may involve signals other than leptin.


Human impacts on the stream-groundwater exchange zone.
Active exchanges of water and dissolved material between the stream and groundwater in many porous sand- and gravel-bed rivers create a dynamic ecotone called the hyporheic zone. Because it lies between two heavily exploited freshwater resources-rivers and groundwater-the hyporheic zone is vulnerable to impacts coming to it through both of these habitats. This review focuses on the direct and indirect effects of human activity on ecosystem functions of the hyporheic zone. River regulation, mining, agriculture, urban, and industrial activities all have the potential to impair interstitial bacterial and invertebrate biota and disrupt the hydrological connections between the hyporheic zone and stream, groundwater, riparian, and floodplain ecosystems. Until recently, our scientific ignorance of hyporheic processes has perhaps excused the inclusion of this ecotone in river management policy. However, this no longer is the case as we become increasingly aware of the central role that the hyporheic zone plays in the maintenance of water quality and as a habitat and refuge for fauna. To fully understand the impacts of human activity on the hyporheic zone, river managers need to work with scientists to conduct long-term studies over large stretches of river. River rehabilitation and protection strategies need to prevent the degradation of linkages between the hyporheic zone and surrounding habitats while ensuring that it remains isolated from toxicants. Strategies that prevent anthropogenic restriction of exchanges may include the periodic release of environmental flows to flush silt and reoxygenate sediments, maintenance of riparian buffers, effective land use practices, and suitable groundwater and surface water extraction policies.


A multiperspective investigation of social competence in children with sickle cell disease.
Compared the social competence and self-perceptions of 4- to 8-year-old children with sickle cell disease (SCD) to a comparison group of healthy children. Social competence ratings were obtained from multiple perspectives, including parents, teachers, and clinic staff members; children provided ratings of self-perceived acceptance and competence. Children in the SCD group were rated as socially competent as their peers in the comparison group and the normative group. Differences across raters were found, however, with parents in the SCD group giving higher ratings than clinic staff members. No differences were revealed between children in the SCD group and the comparison group in their self-perceptions of competence and acceptance. Implications for future studies addressing the situational specificity of social competence and its relevance to health care of chronically ill children are discussed.


Cu2O/Co3O4 nanoarrays for rapid quantitative analysis of hydrogen sulfide in blood.
2D heterostructure nanoarrays have emerged as a promising sensing material for rapid disease detection applications. In this study, a bio-H2S sensor based on Cu2O/Co3O4 nanoarrays was proposed, the controllable preparation of the nanoarrays being achieved by exploring the experimental parameters of the 2D electrodeposition in situ assembly process. The nanoarrays were designed as a multi-barrier system with strict periodicity and long-range order. Based on the interfacial conductance modulation and vulcanization reaction of Cu2O and Co3O4, the sensor exhibited superior sensitivity, selectivity, and stability to H2S in human blood. In addition, the sensor exhibited a reasonable response to 0.1 μmol L-1 Na2S solution, indicating that it had a low detection limit for practical applications. Moreover, first-principles calculations were performed to study changes in the heterointerface during the sensing process and the mechanism of rapid response of the sensor. This work demonstrated the reliability of Cu2O/Co3O4 nanoarrays applied in portable sensors for the rapid detection of bio-H2S.


Neuronal differentiation is accompanied by increased levels of SNAP-25 protein in fetal rat primary cortical neurons: implications in neuronal plasticity and Alzheimer's disease.
Alzheimer's disease (AD) is accompanied by progressive memory loss and decline in general cognitive abilities. Neuropathological hallmarks include amyloid plaque formation, neurofibrillary tangles, and neuronal and synaptic loss. To improve research models in AD, we have characterized several aspects of the primary rat neuronal cell culture model, which relate directly to the study of neuroexocytosis, neuronal plasticity, and amyloidosis. We have attempted to isolate and assess the neuronal enrichment of a primary cortical cell culture by morphological and molecular techniques, following progress of these cultured cells for up to 18 days in culture to identify the optimum timeframe for the manipulation and data collection in these cells. We observed maximum neuronal differentiation around day 15, which was in decline by day 18, thus, the critical window for manipulations in these cultures seems to be between days 12-15. The substantial increase in neuritic length and density was apparent at very early time points and peaked at day 15. In parallel to morphological assessments, we measured levels of a group of selected neuronally important proteins, including cytoskeletal and synaptic proteins. Change in the levels of cell-associated APP and synaptophysin were not as dramatic as that of SNAP-25 or secreted APP. Notably, this increased differentiation is accompanied by a dramatic increase in levels of SNAP-25 protein, which peaked at day 15 and declined thereafter. These results suggest that this neuronal population contains quantifiable presynaptic terminals. Thus, the establishment and molecular characterization of this neuronal model would have many implications in neuroscience research including synaptic differentiation and neuronal plasticity and for the evaluation of pharmacological interventions in the disease process.


A multiprofessional study of patients with myofascial pain-dysfunction syndrome. II.
One hundred and thirteen female patients with myofascial pain-dysfunction (MPD) syndrome were examined by a dentist and a psychiatrist. One hundred and eight of them were also examined by physiotherapists. Particular emphasis was given by the dentist to the types and duration of the chief complaints, the perceived severity of the MPD-symptoms and to the kinds of statements used in the anamnestic reports. Additionally the patients' perceived cause/origin of their symptoms, expectations regarding treatment, reactions to the different types of examination procedures and their reports of perceived daily life stress factors were taken into account. The patients were categorized according to the findings, and the results were compared to the psychiatrist's findings. Some basic clinical patterns were revealed. The results indicate that reports of oral symptoms may have symbolic value. It is concluded that a carefully performed clinical interview may provide the dentist valuable information useful in diagnosis and the choice of treatment.


Effect of pH on aqueous phenylalanine studied using a 265-nm pulsed light-emitting diode.
Recently, we described the characteristics and application of a 265-nm AlGaN light-emitting diode (LED) operated at 1-MHz repetition rate, 1.2-ns pulse duration, 1.32-microW average power, 2.3-mW peak power, and approximately 12-nm bandwidth. The LED enables the fluorescence decay of weakly emitting phenylalanine to be measured routinely in the condensed phase, even in dilute solution. For a pH range of 1-11, we find evidence for a biexponential rather than a monoexponential decay, whereas at pH 13, only a monoexponential decay is present. These results provide direct evidence for the dominance of two phenylalanine rotamers in solution with a photophysics closer to the other two fluorescent amino acids, tyrosine and tryptophan, than has previously been reported. Although phenylalanine fluorescence is difficult to detect in most proteins because of its low quantum yield and resonance energy transfer from phenylalanine to tyrosine and tryptophan, the convenience of the 265-nm LED may well take protein photophysics in new directions, for example, by making use of this resonance energy transfer or by observing phenylalanine fluorescence directly in specific proteins where resonance energy transfer is inefficient.


[Well ageing in the XXI century. Political, social and individual strategies].
Population ageing is a triumph, but because to the tendency to the increase of the phenomenon in all countries of the globe, it is also a concern and a challenge for national governments and societies. Starting from the current picture in the States of European Union and the future predictions, it's provides an overview of the relationship between ageing and health, emphasizing some social, political and person-related aspects. In particular, it's examined the theoretical models, strategies and multilevel actions proposed to well-ageing and with dignity, focusing on the model of "active and healthy ageing" promoted in 2012 by the World Health Organization and the European Union.


Histological and immunohistochemical studies on primary gastrointestinal lymphomas.
To study the characteristics and histogenesis of the malignant lymphomas derived from the gastrointestinal mucosa, histologic and immunohistochemical analyses were performed on a series of 28 malignant lymphomas of the gastrointestinal tract. By cytomorphologic classification, there were two small lymphocytic lymphomas, one small cleaved cell lymphoma, two mixed small cleaved and large cell lymphomas, 17 large cell lymphomas, one small noncleaved cell lymphoma, three immunoblastic lymphomas, and two lymphoblastic lymphomas. This distribution of histologic types was compatible with that of nodal lymphoma. The lymphomas with poor prognostic histology (23 cases) outnumbered those with favorable prognosis (five cases). Three of 28 cases (one in the stomach and two in the small intestine) had cytologic features consistent with centrocytoid cell lymphoma of the mucosa associated lymphoid tissue and were large cell lymphomas. Immunophenotypically, 23 cases expressed B-cell markers (82.1%) and three cases reacted with T-cell markers. Two cases did not react with either T-cell or B-cell markers. True histiocytic lymphomas were not identified. Gastric lymphomas (nine cases) and colorectal lymphomas (three cases) were of B-lymphocyte origin whereas T-cell lymphomas were noted in the small intestine (two cases) and ileocecal region (one case). Three cases of centrocytoid lymphoma were of B-lymphocyte origin. Histologically B-cell lineage lymphomas were evenly distributed on various histologic subtypes but all T-lineage lymphomas belonged to the large cell type. The two cases with undetermined phenotype were lymphoblastic lymphomas histologically. This study showed that the primary GIT lymphomas, mostly of B-cell lineage, were not cytomorphologically distinctive from the nodal lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)


Factors influencing organ placement efforts in donors with brain tumors.
A 3-year retrospective review of brain tumor cases was performed to determine factors that influence organ procurement in light of the increase in references in transplant literature to the hazards of transplanting organs from donors with brain tumors. A 3-year review of cases in which organ procurement efforts occurred were evaluated. Of 314 cases resulting from this review, organ procurement efforts yielded 10 patients with a diagnosis of brain tumor. Of those 10 cases, seven progressed to organ donation, with at least one organ per patient recovered. Manipulation of brain tumors or manipulation along with tissue diagnosis does not seem to hinder procurement of organs. Without tissue diagnosis, the ability of the organ procurement organization to place organs decreases significantly.


Lanthanide(III) complexes with a reinforced cyclam ligand show unprecedented kinetic inertness.
Lanthanide(III) complexes of a cross-bridged cyclam derivative containing two picolinate pendant arms are kinetically inert in very harsh conditions such as 2 M HCl, with no dissociation being observed for at least 5 months. Importantly, the [Ln(dota)](-) complexes, which are recognized to be extremely inert, dissociate under these conditions with lifetimes in the range ca. 1 min to 12 h depending upon the Ln(3+) ion. X-ray diffraction studies reveal octadentate binding of the ligand to the metal ion in the [Eu(cb-tedpa)](+) complex, while (1)H and (13)C NMR experiments in D2O point to the presence of a single diastereoisomer in solution with a very rigid structure. The structure of the complexes in the solid state is retained in solution, as demonstrated by the analysis of the Yb(3+)-induced paramagnetic shifts.


Dilemma of trisomy 20 mosaicism detected prenatally: is it an innocent finding?
The clinical significance of mosaicism trisomy 20 detected prenatally following amniocentesis remains uncertain, due to the rarity of liveborn cases with inconsistent clinical findings, the short postnatal follow-up, and failure in evaluating other fetal tissues for the presence of the trisomy. We report on a 15 month-old 46,XX chromosome constitution in white blood cells, while skin fibroblasts demonstrated trisomy 20 mosaicism (54%) by fluorescence in situ hybridization (FISH) analysis. Clinical examination of the baby showed only minor phenotypic signs (bilateral epicanthal folds, delayed closure of fontanel with no other gross anomalies), but demonstrated a considerable developmental delay in gross and fine motor skills along with hypotonicity. This is the second oldest described liveborn with trisomy 20 mosaicism confirmed in skin fibroblasts. This cytogenetic aberration along with her developmental delay suggests that the two findings are related and that aberration affects various fetal tissues and is not confined to extra-embryonic tissue as suggested previously. Yet, an undiagnosed condition may be the cause of the child's developmental delay. Based on this case and following a review of the literature we suggest that when mosaic trisomy 20 is identified in amniocytes, further evaluation is required. Cord blood should be analyzed preferably by FISH. During counseling the parents should be advised of an additional risk, such as developmental delay, even when fetal cord karyotype and detailed ultrasonic scan are normal.


A rapid, direct observation method to isolate mutants with defects in starch grain morphology in rice.
Starch forms transparent grains, referred to as starch grains (SGs), in amyloplasts. Despite the simple glucose polymer composition of starch, SGs exhibit different morphologies depending on plant species, especially in the endosperm of the Poaceae family. This study reports a novel method for preparing thin sections of endosperm without chemical fixation or resin embedding that allowed us to visualize subcellular SGs clearly. Using this method, we observed the SG morphologies of >5,000 mutagenized rice seeds and were able to isolate mutants in which SGs were morphologically altered. In five mutants, named ssg (substandard starch grain), increased numbers of small SGs (ssg1-ssg3), enlarged SGs (ssg4) and abnormal interior structures of SGs (ssg5) were observed. Amylopectin chain length distribution analysis and identification of the mutated gene suggested a possible allelic relationship between ssg1, ssg2, ssg3 and the previously isolated amylose-extender (ae) mutants, while ssg4 and ssg5 seemed to be novel mutants. Compared with conventional observation methods, the methods developed here are more effective for obtaining fine images of subcellular SGs and are suitable for the observation of a large number of samples.


Deconvolution of UV-VIS spectroelectrochemical thin-layer data for an EE electrochemical process.
A deconvolution method, based on Fixed Size Window Evolving Factor Analysis (FSWEFA) has been developed to analyse the spectroelectrochemical sequence of spectra obtained in OTTLE electrodes for EE electrochemical processes. The analysis of the data permits to reconstruct the concentration profiles, the spectra of the intermediates and an optical analogue of the i vs E curve.


Association between dementia and hepatitis B and C virus infection.
Several viral infections are known to increase the risk of dementia through brain cell damage and systemic infection. The association between hepatitis B and C virus (HBV and HCV) infections and dementia was evaluated using a national sample cohort from South Korea. Using the national cohort study from the Korean National Health Insurance Service, we extracted data for patients with HBV or HCV infection and for matched control participants. The controls were matched to the patients according to age, sex, income, region of residence, and past medical histories. The incidence of HCV infection was higher in the dementia group (1.0% [113/11,228]) than in the control group (0.8% [364/44,912], P = .043). However, there was no difference in the incidence of HBV infection in the dementia and control groups. The adjusted odds ratio (OR) for HCV infection was 1.25 (95% confidence interval [CI] = 1.01-1.54, P = .043) in the dementia group. According to the subgroup analysis by sex, the adjusted ORs for HCV infection were 1.04 (95% CI = 072-1.49, P = .851) in men and 1.38 (95% CI = 1.06-1.79, P = .016) in women. We concluded that the incidence of HCV infection was higher (with a higher OR) in women with dementia than in matched control participants in South Korea.


18F-FDG PET/CT Osteometabolic Activity in Metastatic Parathyroid Carcinoma.
Parathyroid cancer is an uncommon type of malignancy, which is frequently associated with poor prognosis. Clinical manifestations are caused by elevated serum calcium and parathyroid hormone (PTH). Diagnostic imaging studies as neck ultrasonography, technetium Tc Tc-sestamibi whole body scintigraphy, CT, and MR are already established tools for this malignancy. Nevertheless, the role of F-FDG PET/CT remains unknown in this scenario, with few published studies in literature. Hence, in this article, we aimed to report an illustrative case of increased skeletal FDG uptake associated with high calcium and PTH levels.


What about Us? Economic and Policy Changes Affecting Rural HIV/AIDS Services and Care.
Health care budgets and policies are chief drivers in the delivery and access to health services. Place is also a factor that affects patient and provider experiences within the health care system. We examine the impact of policy changes and subsequent budget cuts on rural HIV/AIDS care, support services, and prevention. We interviewed 11 social workers, case managers, and outreach workers who serve rural people living with HIV/AIDS. We conducted telephone interviews inquiring about the effect of economics and policies on direct practice with rural clients. We analyzed data using a content analysis approach. We found several themes from the data. Ryan White funding and policy changes shifted direct practice to a medical case management model. Changes in federal and state poverty levels affected client eligibility for the AIDS Drugs Assistance Program. Policy banning financial support for syringe service programs hindered prevention efforts to reduce HIV/AIDS transmission. Ancillary services were reduced, such as housing assistance, transportation, and emergency financial assistance. In conclusion, we highlight the importance of place-based policies to improve access to healthcare and services. We also provide recommendations for greater inclusion in HIV/AIDS-related policy development, care, and service planning for rural workers.


DNA methylation patterns in adenomas from FAP, multiple adenoma and sporadic colorectal carcinoma patients.
Colorectal adenomas have traditionally been regarded as homogeneous. The aim of our study was to identify molecular features that may differentiate sporadic adenomas from familial adenomas such as Familial Adenomatous Polyposis (FAP) and Multiple Adenoma patients. DNA methylation was tested at Methylated IN Tumor (MINT) loci (1,2,12,31) and the CpG promoter region of genes MLH1, HPP1, MGMT, p14ARF and p16INK4a in FAP-associated adenomas (33) from 5 patients with a known APC mutation (Group 1, FAP), adenomas (29) from 4 Multiple Adenoma patients (Group 2 Multiple), adenomas (14) from 3 patients with sporadic colorectal cancers showing high microsatellite instability (Group 3, MSI-H) and adenomas (16) from 7 patients, with sporadic colorectal cancers showing microsatellite stable or low level instability (Group 4, MSS/MSI-L). Aberrant Crypt Foci (ACFs), Hyperplastic Polyps (HPs) and cancers were also examined for methylation status as well as K-ras mutation. Multiple Adenoma patients were examined for germline polymorphisms in the base excision repair gene, MYH. The familial syndrome, FAP -associated adenomas showed a significantly low frequency of MINT methylation (15.5%,) compared to sporadic MSS/MSI-L-associated adenomas (35.5%). Group 3 (MSI-H) adenomas were different in that many showed serration and a high level of methylation (57.1%). Group 2, Multiple Adenoma cases, resembled sporadic MSS/MSI-L-associated adenomas. However the promoter regions of key genes, MGMT, p14ARF and p16INK4a were methylated to a greater extent than MINTs in both sporadic and familial adenomas. Genetic profiling of adenomas supports the concept that adenomas belonging to familial syndromes pursue a different pathway to tumorigenesis than their sporadic counterpar/ts from their earliest formation.


Cold-sensitive ribosome assembly in an Escherichia coli mutant lacking a single methyl group in ribosomal protein L3.
Ribosomal protein methylation has been well documented but its function remains unclear. We have examined this phenomenon using an Escherichia coli mutant (prmB2), which fails to methylate glutamine residue number 150 of ribosomal protein L3. This mutant exhibits a cold-sensitive phenotype: its growth rate at 22 degrees C is abnormally low in complete medium. In addition, strains with this mutation accumulate abnormal and unstable ribosomal particles; 50-S and 30-S subunits are formed, but at a lower rate. Once assembled, ribosomes with unmethylated L3 are fully active by several criteria. (a) Protein synthesis in vitro with purified 70-S prmB2 ribosomes is as active as wild-type using either a natural (R17) or an artificial [poly(U)] messenger. (b) The induction of beta-galactosidase in vivo exhibits normal kinetics and the enzyme has a normal rate of thermal denaturation. (c) These ribosomes are standard when exposed in vitro to a low magnesium concentration or increasing molarities of LiCl. Efficient methylation of L3 in vitro requires either unfolded ribosomes or a mixture of ribosomal protein and RNA. We suggest that the L3-specific methyltransferase may qualify as one of the postulated 'assembly factors' of the E. coli ribosome.


Effects of estradiol on high-voltage-activated Ca(2+) channels in cultured rat cortical neurons.
Estrogen regulates a wide variety of nonreproductive functions in the central nervous system. Cortical neurons contain a diverse range of voltage-gated ion channels, including calcium (Ca(2+)) channels, and Ca(2+) channels play an important role in the regulation of action potential generation and neuronal excitability. In this study, the effect of estradiol (E2) on high-voltage-activated (HVA) Ca(2+) channels in cultured rat cortical neurons was examined. We used the whole-cell patch-clamp technique to measure the HVA Ca(2+) channels. We found that HVA Ca(2+) channel currents was inhibited by 17β-E2 in a rapid, reversible and concentration-dependent manner. Moreover, 17β-E2 shifted the steady-state inactivation curve in the hyperpolarizing direction without changing the activation curve. We also found that the inhibitory effects of 17β-E2 on Ca(2+) currents were unaffected by the estrogen receptor (ER) antagonist ICI 182780; however, the protein kinase C (PKC) inhibitor rottlerin and protein kinase A (PKA) inhibitor H-89 blocked the 17β-E2-induced inhibition of Ca(2+) currents. E2 inhibited HVA Ca(2+) currents via PKC and PKA-dependent signaling pathway in cortical neurons, and the effects of BPA were independent of classical ER.


Automatic estimation of corneal nerves focused tortuosities.
The correlation between corneal nerve tortuosity and pathology has been shown multiple times. However, because there isn't any defacto definition of tortuosity, reproducibility is poor. Indeed, many studies still rely on the manual observation and judgment of tortuosity. Recently, two distinct forms of corneal nerve tortuosity have been identified, describing either short-range or long-range directional changes. In this study we were able to develop automatic corneal nerve tortuosity measurements that correctly and independently represent these two tortuosity definitions. Furthermore, we show that a combination of mathematical tortuosity measurements improves on single metric results.


Biochemical and Structural Characterization of Human Core Elongator and Its Subassemblies.
Conserved from yeast to humans and composed of six core subunits (Elp1-Elp6), Elongator is a multiprotein complex that catalyzes the modification of the anticodon loop of transfer RNAs (tRNAs) and in turn regulates messenger RNA decoding efficiency. Previous studies showed that yeast Elongator consists of two subassemblies (yElp1/2/3 and yElp4/5/6) and adopts an asymmetric overall architecture. Yet, much less is known about the structural properties of the orthologous human Elongator. Furthermore, the order in which the different Elongator subunits come together to form the full assembly as well as how they coordinate with one another to catalyze tRNA modification is not fully understood. Here, we purified recombinant human Elongator subunits and subassemblies and examined them by single-particle electron microscopy. We found that the human Elongator complex is assembled from two subcomplexes that share similar overall morphologies as their yeast counterparts. Complementary co-purification and pulldown assays revealed that the scaffolding subunit human ELP1 (hELP1) has stabilizing effects on the human ELP3 catalytic subunit. Furthermore, the peripheral hELP2 subunit appears to enhance the integrity and substrate-binding ability of the dimeric hELP1/2/3. Lastly, we found that hELP4/5/6 is recruited to hELP1/2/3 via hELP3. Collectively, our work generated insights into the assembly process of core human Elongator and the coordination of different subunits within this complex.


Aurum: a case study in the politics of NIMBY.
The literature on the phenomenon of community resistance to local siting of undesirable facilities, the so-called ;not in my backyard' syndrome (NIMBY), emphasizes community civic characteristics and motivation. We describe a case study in which prior political history played an important but not obvious role. The Aurum project was a proposed landfill for the city of Edmonton, Alberta (Canada) proposed in 1989 and 1990 for an isolated and mostly vacant site within city limits but across a river from the developed area. The siting was bitterly but successfully opposed by the government and residents of the adjacent area. Investigation determined residual, unspoken resentment among county residents against an attempt by the city to annex it decades before. It was concluded that in this instance, and probably many others, the political history of the community plays a major role in conditioning their response to ;locally undesirable land use' (LULUs) and the NIMBY phenomenon.


Node-Negative Esophageal Cancer With Short-Interval Isolated Metastasis to the Gallbladder: A Case Report.
A 55 year old male smoker presented with clinical T3N0 esophageal adenocarcinoma of the GE junction. He completed neoadjuvant chemoradiotherapy with carboplatin/paclitaxel and 5040cGy of radiation. He had limited clinical response on restaging but no evidence of metastatic disease and completed a minimally invasive three field esophagectomy. This was complicated by a chyle leak requiring thoracic duct embolization from which he recovered well. Surgical pathology showed no apparent nodal disease or metastases but a poorly differentiated primary tumor with signet-cell features. Approximately 3 months after his surgery, he developed right upper quadrant abdominal pain and elevated liver function tests and was taken for laparoscopic cholecystectomy. Gallbladder pathology demonstrated poorly differentiated adenocarcinoma with extensive lymphovascular invasion with immunohistochemistry analysis and comparison with the original surgical specimen confirming metastatic adenocarcinoma of esophageal origin. Literature review suggests that signet cell features and limited response to neoadjuvant therapy point to a more aggressive biology in esophageal cancer and increase the risk of metastatic disease, even in the setting of node negativity.


Direct reduction of nitrite to N2 on a Pt(100) electrode in alkaline media.
The selective reduction of NO(2)(-) to N(2) in 0.1 M NaOH was obtained at a Pt(100) electrode in a narrow but distinct potential region. This is the first report of such selectivity for this reaction on Pt(100), which is known to be the most catalytically active platinum surface toward NO(2)(-) reduction in alkaline media. Both ammonia and nitrous oxide are ruled out as possible reaction intermediates on the basis of online electrochemical mass spectrometry. Based on earlier work on ammonia oxidation, NH(2) adsorbates are speculated to be involved in the reaction mechanism.


Natural Tyrosinase Inhibitors: Role of Herbals in the Treatment of Hyperpigmentary Disorders.
Cutaneous pigmentation plays critical role in determining the color of skin along with photo protection of skin from dreadful effects of ultraviolet radiations. Conversely, abnormal accumulation of melanin is responsible for hyper pigmentary disorders such as melasma, senile lentigines and freckles. Because of the visible nature of dermatologic diseases, they have a considerable psychosomatic effect on affected patients. Tyrosinase inhibitors are molecules that interrelate in some way with the enzyme to prevent it from working in the normal manner. Past many decades witnessed the quest for the development of natural tyrosinase inhibitors due to imperative role played by tyrosinase in the process of melanogenesis and fungi or fruit enzymatic browning. Mechanism of pigmentation is characterized by the intact process of the synthesis of specialized black pigment within melanosomes. Melanin is synthesized by a cascade of enzymatic and chemical reactions. For this reason, melanin production is mainly controlled by the expression and activation of tyrosinase. In the current article, we discussed tyrosinase inhibitors from the natural sources, which can be an essential constituent of cosmetics products and depigmenting agents for the treatment of hyperpigmentory disorders.


Climate change negates positive CO2 effects on marine species biomass and productivity by altering the strength and direction of trophic interactions.
One of the biggest challenges in more accurately forecasting the effects of climate change on future food web dynamics relates to how climate change affects multi-trophic species interactions, particularly when multiple interacting stressors are considered. Using a dynamic food web model, we investigate the individual and combined effect of ocean warming and acidification on changes in trophic interaction strengths (both direct and indirect) and the consequent effects on biomass structure of food web functional groups. To do this, we mimicked a species-rich multi-trophic-level temperate shallow-water rocky reef food web and integrated empirical data from mesocosm experiments on altered species interactions under warming and acidification, into food-web models. We show that a low number of strong temperature-driven changes in direct trophic interactions (feeding and competition) will largely determine the magnitude of biomass change (either increase or decrease) of high-order consumers, with increasing consumer biomass suppressing that of prey species. Ocean acidification, in contrast, alters a large number of weak indirect interactions (e.g. cascading effects of increased or decreased abundances of other groups), enabling a large increase in consumer and prey biomass. The positive effects of ocean acidification are driven by boosted primary productivity, with energy flowing up to higher trophic levels. We show that warming is a much stronger driver of positive as well as negative modifications of species biomass compared to ocean acidification. Warming affects a much smaller number of existing trophic interactions, though, with direct consumer-resource effects being more important than indirect effects. We conclude that the functional role of consumers in future food webs will be largely regulated by alterations in the strength of direct trophic interactions under ocean warming, with ensuing effects on the biomass structure of marine food webs.


Plasma oxidants and antioxidants in acute ischaemic stroke.
Plasma levels of the oxidants xanthine oxidase, nitric oxide and malondialdehyde and the antioxidants superoxide dismutase, glutathione peroxidase and glutathione reductase, together with total superoxide scavenger activity and non-enzymatic superoxide scavenger activity, were determined in 19 patients with acute ischaemic stroke and 20 controls. Compared with controls, superoxide dismutase, total superoxide scavenger activity, glutathione peroxidase and glutathione reductase activities were significantly lower, and nitric oxide and malondialdehyde levels significantly higher, in acute stroke patients. Xanthine oxidase showed a slight but non-significant increase in stroke patients compared with controls. There was no significant difference in non-enzymatic superoxide scavenger activity between the two groups. There was a positive correlation between glutathione reductase levels and Glasgow Coma Scale scores, and a negative correlation between malondialdehyde levels and non-enzymatic superoxide scavenger activity. These findings suggest that oxidative stress in patients with acute ischaemic stroke may be the result of an imbalance in oxidant/antioxidant homeostasis.


Ligand-controlled iron-catalyzed coupling of α-substituted β-ketoesters with phenols.
A chemo-, regio-, and stereoselective FeCl(3)/1,10-phenanthroline-catalyzed cross dehydrogenative coupling (CDC) reaction between phenols and α-substituted β-ketoesters was developed. The reaction creates a new quaternary carbon center within a polycyclic hemiacetal or polycyclic spirolactone architecture. The applicability of the new method to the synthesis of natural products was demonstrated by a possible biomimetic synthesis of the lachnanthospirone core.


Isolation and characterization by NMR spectroscopy of three monosubstituted 4-sulfobutyl ether derivatives of cyclomaltoheptaose (beta-cyclodextrin).
The substitution profile of 4-sulfobutyl ether derivatives of cyclomaltoheptaose (beta-cyclodextrin) (SBE-beta-CD) prepared in our laboratories has been previously described. However, in those studies, no attempt was made to characterize the positional or regional isomers of this material. SBE-beta-CD derivatives with degrees of substitution of two or higher represent a large number of possible isomers dependent on this positional and regional substitution. The monosubstituted SBE derivative, however, cannot have regional isomers and, therefore, has only three possible substitution products related to the 2-, 3-, and 6-hydroxyl groups of a glucose unit. In this study the isomers were fractionated by preparative anion-exchange chromatography with the progress of the elution being followed by a capillary electrophoretic (CE) method that resolved these isomers. The eluent containing the isomers was processed, and the pure materials were characterized by nuclear magnetic resonance spectroscopy (1H NMR, DEPT, HETCOR, HOHAHA). Through this analysis the assignment of the positional isomers was made.


Clinical trials of rotavirus vaccines.
The clinical efficacy of candidate rotavirus vaccines has been tested in Tampere, Finland, over four winter and spring rotavirus epidemic seasons in 1983-1986. Testing against natural challenge has demonstrated that heterologous oral rotavirus vaccines induce cross-protection to human rotavirus diarrhoea. The trials have also given insight into mechanisms of protection in human rotavirus diarrhoea. After the oral vaccination of infants aged six to 12 months the highly attenuated bovine rotavirus strain RIT 4237, titre 10(8) per dose, probably 'takes' in most vaccinees, producing a symptomless intestinal infection with a low virus excretion rate and an antibody response in over 80% of the initially seronegative subjects. Upon natural challenge such vaccination gives no protection against human rotavirus infection but gives 50-60% protection against any clinically detectable rotavirus-associated illness and 80-90% protection against severe rotavirus diarrhoea, regardless of the infecting human rotavirus serotype. The less attenuated rhesus monkey rotavirus RRV-1, titre 10(5)-10(6) per dose, is more infectious in humans, and virus multiplication in the intestine results in excretion of vaccine virus in the stools and some clinical symptoms, mainly fever, 3-4 days after vaccination. The degree of protection against human rotavirus diarrhoea appears similar to that induced by bovine rotavirus vaccine.


Genetic and pharmacologic abrogation of Snail1 inhibits acinar-to-ductal metaplasia in precursor lesions of pancreatic ductal adenocarcinoma and pancreatic injury.
Pancreatic cancer (PDAC) is one of the most dismal of human malignancies. Inhibiting or delaying the progression of precursor lesions of PDAC, pancreatic intraepthial neoplasia (PanINs), to invasive cancer, would be a major step. In the present study, we used a transgenic murine model of pancreatic cancer to evaluate the impact of a conditional knockout of the transcription factor Snail1, a major factor in epithelial-to-mesenchymal transition, on acinar-to-ductal formation and on PanIN progression. By interbreeding conditional LsL-Snail floxf/wt ; LsL-Kras G12D and Pdx1-Cre strains, we obtained LsL-Kras G12D ;Pdx1-Cre(KP) mice, Snail1 heterozygous knockout LsL-Kras G12D ; LsL-Snail flox/- ;Pdx1-Cre(KPShet) mice or Snail1 homozygous knockout LsL-Kras G12D ;LsL-Snail flox/flox ;Pdx1-Cre(KPS) mice. Mice were then followed in a longitudinal study for 2, 4, 6, 8, 10, and 12 months. Furthermore, in mice with a genetic or pharmacological inhibition of Snail1, using the Snail1 inhibitor GN25, a model of pancreatic injury by administration of cerulein was introduced to evaluate ADM formation in this setting. A translational approach with a tissue microarray (TMA) of human PanINs and an in vivo nude mouse platform to test GN25 in human pancreatic adenocarcinoma was then adopted. Quantification of PanINs showed delayed initiation and progression of PanIN lesions at all ages in both homozygous and heterozygous Snaildel1;Pdx-1-Cre;LSL-KrasG12D/+-Mice. PanINs at TMA revealed snail expression in the majority of cases. GN25 showed growth inhibition in 2/2 human pancreatic adenocarcinomas using a nude mice in vivo platform. Genetic and pharmacologic abrogation of Snail1 signaling in exocrine pancreas impairs development of acinar-to-ductal metaplasia following cerulein-mediated pancreatic injury. The present study suggests a fundamental new approach to delay the progression of PDAC.


Comprehensive evaluation of growth performance and meat characteristics of a fattening system combining grazing with feeding rice whole-crop silage in Japanese Black steers.
We investigated the effect of a system for fattening steers combining grazing with feeding rice whole-crop silage (rWCS) on growth performance, meat characteristics, and the expression of genes involved in skeletal muscle growth. Steers were randomly assigned to grazing or concentrate-fed groups (CT). The grazing group (GZ) was fed rWCS after grazing until 16 months of age. The final body weight was the same in the two groups, but the dressed weight was lower in the GZ than in the CT. The beef color standard was higher in the GZ than in the CT. Although beef marbling did not differ between the two groups, there was less intramuscular fat and subcutaneous fat in the GZ than in the CT. The α-tocopherol and β-carotene contents in the muscle were higher in the GZ than in the CT. The GZ showed a lower daily gain (DG) during the grazing period, which may have resulted from decelerating skeletal muscle growth caused by the increased expression of genes encoding myostatin and atrogin-1. However, the DG and feed efficiency of the GZ increased after grazing. The two groups exhibited a similar level of beef productivity.


Measurement of 3-D displacement: sandwich holography and regulated path length interferometry.
An analysis of sandwich and regulated path length interferometries is used to determine 3-D displacement. The combination of the two techniques provides a reliable means for unambiguous determination of displacement. To demonstrate the efficiency of the combination displacement measurement is made of object surface points on a steel beam. The accuracy of sandwich hologram interferometry is replicable for a series of measurements and does not fall below the value needed in industrial measurements.


Deterministic and stochastic regimes of asexual evolution on rugged fitness landscapes.
We study the adaptation dynamics of an initially maladapted asexual population with genotypes represented by binary sequences of length L. The population evolves in a maximally rugged fitness landscape with a large number of local optima. We find that whether the evolutionary trajectory is deterministic or stochastic depends on the effective mutational distance d(eff) up to which the population can spread in genotype space. For d(eff) = L, the deterministic quasi-species theory operates while for d(eff) < 1, the evolution is completely stochastic. Between these two limiting cases, the dynamics are described by a local quasi-species theory below a crossover time T(x) while above T(x) the population gets trapped at a local fitness peak and manages to find a better peak via either stochastic tunneling or double mutations. In the stochastic regime d(eff) < 1, we identify two subregimes associated with clonal interference and uphill adaptive walks, respectively. We argue that our findings are relevant to the interpretation of evolution experiments with microbial populations.


Preventive effect of oren-gedoku-to (huanglian-jie-du-tang) extract on progression of carbon tetrachloride-induced acute liver injury in rats.
The effect of oral administration of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract (TJ-15) on the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4). When TJ-15 at a dose of 500 mg/kg body weight (b.w.) was administered to male Wistar rats aged seven weeks 6 hours after i.p. injection of CCl4 (1.0 ml/kg b.w.), an apparent liver injury occurred. Significant prevention against the progression of liver injury was found 24 hours after the injection judging from the activities of serum transaminases and other indices of liver cell damage. An increase in lipid peroxide level and decreases in reduced glutathione level and superoxide dismutase (SOD) activity occurred in the liver at 6 and 24 hours after CCl4 injection. Serum SOD activity increased 24 hours after CCl4 injection. Post-oral TJ-15 administration significantly ameliorated all these changes found at 24 hours after CCl4 injection. An increase in liver triglyceride level and a decrease in serum triglyceride level also occurred 6 and 24 hours after CCl4 injection. Post-oral TJ-15 administration prevented the increase in liver triglyceride level at 24 hours after CCl4 injection. Although the activity of liver tryptophan 2,3-dioxygenase (TDO), a marker of the inhibition of liver protein synthesis by CCl4, decreased 6 and 24 hours after injection of the toxicant, post-oral TJ-15 administration had no effect on this decrease in TDO activity at 24 hours after the injection. These results indicate that oral TJ-15 administration can prevent the progression of acute liver injury in CCl4-injected rats, and suggest that this prevention could be due to the action of TJ-15 to scavenge free radicals formed in the liver and to inhibit triglyceride accumulation in the liver.


Learnings From a Pilot Study to Strengthen Primary Health Care Services: The Community-Clinic-Centered Health Service Model in Barishal District, Bangladesh.
Community clinics (CCs) staffed by community health workers (CHWs) represent an effort of the Government of Bangladesh to strengthen the grassroots provision of primary health care services and to accelerate progress in achieving universal health coverage. The Improving Community Health Workers (ICHWs) Project of Save the Children piloted a CC-centered health service (CCHS) model that strengthened community and local government engagement, harmonized the work of different CHW cadres who were working in the same catchment area of each CC, and improved the accountability of CHWs and the CC to the local community. We describe the process for developing and implementing the CCHS model in 6 unions in Barishal District where the model was piloted and provide some early qualitative and quantitative findings pertaining to the model's effectiveness. Data were collected from CCs in the 6 pilot unions and 6 other unions that served as a control. Qualitative data were collected from the intervention area during the pre-pilot (October 2017-September 2018) and pilot phase (October 2018-September 2019). Document review, key informant interviews, and focus group discussions were also conducted. Maternal and child health service utilization data were extracted from the government health information system in both the intervention and control areas. Community group meetings ensured engagement with local government authorities and supported resource mobilization. There was greater coordination of work among CHWs and increased motivation of CHWs to better serve their clients. The analysis showed that the increase in maternal health consultations was substantially greater in the intervention area than in the control area, as was the number of referrals for higher-level care. The CCHS model as applied in this pilot project is effective in engaging local key stakeholders, increasing CHW capacity, and improving client satisfaction. The model demonstrated that a community health system can be strengthened by a comprehensive approach that engages communities and local government officials and that harmonizes the work of CHWs.


The Role of Sclerostin in Bone and Ectopic Calcification.
Sclerostin, a 22-kDa glycoprotein that is mainly secreted by the osteocytes, is a soluble inhibitor of canonical Wnt signaling. Therefore, when present at increased concentrations, it leads to an increased bone resorption and decreased bone formation. Serum sclerostin levels are known to be increased in the elderly and in patients with chronic kidney disease. In these patient populations, there is a high incidence of ectopic cardiovascular calcification. These calcifications are strongly associated with cardiovascular morbidity and mortality. Although data are still controversial, it is likely that there is a link between ectopic calcification and serum sclerostin levels. The main question, however, remains whether sclerostin exerts either a protective or deleterious role in the ectopic calcification process.


A randomized clinical trial of neurally adjusted ventilatory assist versus conventional weaning mode in patients with COPD and prolonged mechanical ventilation.
Patient-ventilator asynchrony is a common problem in mechanically ventilated patients; the problem is especially obvious in COPD. Neutrally adjusted ventilatory assist (NAVA) can improve patient-ventilator asynchrony; however, the effect in COPD patients with prolonged mechanical ventilation is still unknown. The goals of this study are to evaluate the effect of NAVA and conventional weaning mode in patients with COPD during prolonged mechanical ventilation. The study enrolled a total of 33 COPD patients with ventilator dependency for more than 21 days in the weaning center. A diaphragm electrical activity (Edi) catheter was inserted in patients within 24 hours after admission to the respiratory care center, and patients were randomly allocated to NAVA or conventional group. A spontaneous breathing trial was performed every 24 hours. The results correlated with the clinical parameters. There were significantly higher asynchrony incidence rates in the whole group after using Edi catheter (before vs post-Edi catheter insertion =60.6% vs 87.9%, P<0.001). Asynchrony index: before vs post-Edi catheter insertion =7.4%±8.5% vs 13.2%±13.5%, P<0.01. Asynchrony incidence: NAVA vs conventional =0% vs 84.2%, P<0.001. Asynchrony index: NAVA vs conventional =0 vs 11.9±11.2 (breath %), P<0.001. The most common asynchrony events were ineffective trigger and delayed trigger. Compared to conventional mode, NAVA mode can significantly enhance respiratory monitoring and improve patient-ventilator interaction in COPD patients with prolonged mechanical ventilation in respiratory care center.


Comparison of a new commercial test, Dermatophyte-PCR kit, with conventional methods for rapid detection and identification of Trichophyton rubrum in nail specimens.
The performance of a new commercially available duplex PCR, which combines pan-dermatophyte PCR with a Trichophyton rubrum-specific PCR, was evaluated. This Dermatophyte PCR kit, which requires one day for laboratory diagnosis, was compared with the conventional methods of microscopy and culture that necessitate up to 4 weeks for final diagnosis of dermatophytosis. We studied 177 nail samples from patients with suspected onychomycosis by fluorescence microscopy (blankophore), cultures and the Dermatophyte PCR kit. More samples were positive by PCR (78/177, 44%) than by culture (59/177, 34%). T. rubrum was present in 95% of all culture-positive nail specimens, which was confirmed by PCR in 55/56 specimens. The positive predictive value, negative predictive value, specificity and sensitivity of the duplex PCR was 93%, 87%, 94% and 85%, respectively, when confirmed by positive culture, microscopy or both. Due to its sensitivity, specificity and rapidity, we conclude that this PCR is an attractive method for routine investigation of nail dermatophytosis in a clinical setting.


The mannoprotein of Saccharomyces cerevisiae is an effective bioemulsifier.
The mannoprotein which is a major component of the cell wall of Saccharomyces cerevisiae is an effective bioemulsifier. Mannoprotein emulsifier was extracted in a high yield from whole cells of fresh bakers' yeast by two methods, by autoclaving in neutral citrate buffer and by digestion with Zymolase (Miles Laboratories; Toronto, Ontario, Canada), a beta-1,3-glucanase. Heat-extracted emulsifier was purified by ultrafiltration and contained approximately 44% carbohydrate (mannose) and 17% protein. Treatment of the emulsifier with protease eliminated emulsification. Kerosene-in-water emulsions were stabilized over a broad range of conditions, from pH 2 to 11, with up to 5% sodium chloride or up to 50% ethanol in the aqueous phase. In the presence of a low concentration of various solutes, emulsions were stable to three cycles of freezing and thawing. An emulsifying agent was extracted from each species or strain of yeast tested, including 13 species of genera other than Saccharomyces. Spent yeast from the manufacture of beer and wine was demonstrated to be a possible source for the large-scale production of this bioemulsifier.


[Bone metastases : New aspects of pathogenesis and systemic therapy].
The occurrence of bone metastases, in particular secondary to breast and prostate cancer, represents a complex medical condition that is debilitating for affected patients. In order to provide an efficient and personalized therapy, an interdisciplinary treatment approach is mandatory; therefore, systemic pharmacological therapy represents a core element of the overall treatment concept. In terms of pathophysiology, the cancer cells cause a massive disturbance of the local bone microenvironment, which as a rule leads to activation of bone resorbing osteoclasts. In addition to bisphosphonates, which can be considered classical antiresorptive agents, the monoclonal receptor activator of nuclear factor-kappa B ligand (RANKL) antibody denosumab has been in use in clinical practice since 2011. The alpha-emitting radioisotope Alpharadin was also recently approved for the treatment of metastatic prostate cancer. This article provides a summary of the most recent knowledge on the pathogenesis of how cancer cells alter the bone microenvironment as well as a review of established and future systemic treatment options.


Pharmacogenetics of warfarin: current status and future challenges.
Warfarin is an anticoagulant that is difficult to use because of the wide variation in dose required to achieve a therapeutic effect, and the risk of serious bleeding. Warfarin acts by interfering with the recycling of vitamin K in the liver, which leads to reduced activation of several clotting factors. Thirty genes that may be involved in the biotransformation and mode of action of warfarin are discussed in this review. The most important genes affecting the pharmacokinetic and pharmacodynamic parameters of warfarin are CYP2C9 (cytochrome P(450) 2C9) and VKORC1 (vitamin K epoxide reductase complex subunit 1). These two genes, together with environmental factors, partly explain the interindividual variation in warfarin dose requirements. Large ongoing studies of genes involved in the actions of warfarin, together with prospective assessment of environmental factors, will undoubtedly increase the capacity to accurately predict warfarin dose. Implementation of pre-prescription genotyping and individualized warfarin therapy represents an opportunity to minimize the risk of haemorrhage without compromising effectiveness.


An Integrated Process for Co-Developing and Implementing Written and Computable Clinical Practice Guidelines.
The goal of this article is to describe an integrated parallel process for the co-development of written and computable clinical practice guidelines (CPGs) to accelerate adoption and increase the impact of guideline recommendations in clinical practice. From February 2018 through December 2021, interdisciplinary work groups were formed after an initial Kaizen event and using expert consensus and available literature, produced a 12-phase integrated process (IP). The IP includes activities, resources, and iterative feedback loops for developing, implementing, disseminating, communicating, and evaluating CPGs. The IP incorporates guideline standards and informatics practices and clarifies how informaticians, implementers, health communicators, evaluators, and clinicians can help guideline developers throughout the development and implementation cycle to effectively co-develop written and computable guidelines. More efficient processes are essential to create actionable CPGs, disseminate and communicate recommendations to clinical end users, and evaluate CPG performance. Pilot testing is underway to determine how this IP expedites the implementation of CPGs into clinical practice and improves guideline uptake and health outcomes.


Calcineurin inhibitor avoidance versus steroid avoidance following kidney transplantation: Postoperative complications.
This study compared early postoperative complications in kidney transplant recipients treated with either a sirolimus-based calcineurin inhibitor (CNI)-free regimen or a tacrolimus-based steroid-free regimen. We used a single-center, prospective, sequential but nonrandomized study design. Consecutive recipients of primary cadaveric or non-HLA identical kidney transplant recipients received either a CNI-free regimen, consisting of sirolimus 5 mg daily beginning postoperative day 3, mycophenolate mofetil 1 gm twice a day, and methylprednisolone 500 mg intraoperatively, then prednisone 30 mg daily tapered to 10 mg daily at 3 months, or a prednisone-free regimen, consisting of methylprednisolone 500 mg, 250 mg, and 125 mg from days 0 to 2, then no further steroids, tacrolimus 0.075 mg/kg twice a day, and mycophenolate mofetil 1 g twice a day. All patients received thymoglobulin induction 6 mg/kg total dose. Outcome measures were patient and graft survival, BPAR, surgical and wound complications, viral infections and posttransplant diabetes mellitus (PTDM). Both groups had excellent early outcomes with no significant difference in patient or graft survival, early renal function, BPAR, surgical or wound complications, or viral infections between the two groups. Patients in the sirolimus-based CNI-free group had a significantly higher incidence of PTDM and a trend toward more discontinuation due to drug toxicity. Whether either regimen improves long-term outcomes awaits longer follow-up.


Is psychosis in DSM-IV mania due to severity? The relevance of selected demographic and comorbid social-phobic features.
We tested whether factors other than episode severity contributed to psychosis in mania. Psychiatrists collected systematic clinical data on 1090 hospitalized DSM-IV manic patients in France, and completed the Mania Rating Scale (MRS) and the Scale for the Assessment of Positive Symptoms (SAPS). Using DSM-IV specifiers, 21.9% were non-severe, 28.2% severe without psychosis, and 49.9% severe with psychosis. On the MRS, patients with psychosis scored significantly higher (P < 0.0001) than non-severe, but did not differ from the severe without psychosis. We found significant correlations between both the Hallucination and the Delusion subscores of the SAPS and the MRS, as well as correlations between age, single marital status, comorbid social phobia and psychotic mania. Apart from episode severity, social isolation - associated with younger age, single marital status and social phobia - seems to make a contribution to the origin of manic psychosis largely independent from such severity.


[Type 2 Diabetes and Vascular Endothelial Dysfunction].
Vascular endothelial function is important for maintaining the homeostasis of the living body. Especially, nitric oxide (NO) produced in vascular endothelial cells regulates blood vessel tone and has an antiatherosclerotic effect. Type 2 diabetes is a typical disease that causes impaired vascular endothelial function, resulting in various vascular complications and damage to organs. Cardiovascular disease associated with type 2 diabetes is a chronic inflammatory disease that starts with endothelial dysfunction (ED), and vascular ED is important as an initial change in arteriosclerotic lesions. Vascular ED in type 2 diabetes is thought to be caused by hyperglycemia, hyperinsulinemia associated with insulin resistance, and hypoglycemia, in which elevated oxidative stress accompanying postprandial hyperglycemia and blood glucose fluctuation are involved. Vascular ED is also caused by postprandial metabolic abnormalities, so correcting postprandial metabolic abnormalities is also important. Meanwhile, Glucagon-like peptide-1 (GLP-1) receptor agonist, thiazolidine, biguanide and Dipeptidyl peptidase-4 (DPP-4) inhibitor have an effect of protecting vascular endothelial function beyond glycemic control. In order to promote a healthy lifestyle for diabetes patients, it is important not only to lower HbA1c but also to avoid postprandial hyperglycemia, blood glucose fluctuation, and hypoglycemia. It is also important to conduct treatment with a view to suppressing vascular complications, such as the selection of antiarteriosclerosis medications.


Hypoglycemic coma due to insulin autoimmune syndrome induced by methimazole: A rare case report.
Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the presence of insulin-binding autoantibodies and fasting or late postprandial hypoglycemia. The number of reports on the association of human leukocyte antigen (HLA) genotype with this disease in adolescents in China is limited. This is the case report of a 17-year-old female patient with Graves' disease who was treated with methimazole (MTZ). After 4 weeks of continuous MTZ treatment, the patient suffered an episode of unconsciousness during the late postprandial phase and was admitted to the hospital, where the blood glucose level was found to be 2.88 mmol/l. The symptoms were relieved following intravenous glucose administration. Imaging studies of the pancreas were unremarkable, but the laboratory investigations on admission revealed high serum levels of total insulin, associated with relatively low levels of free insulin and markedly elevated insulin autoantibody (IAB) levels. HLA testing revealed DRB1*0406/0901 and the patient discontinued MTZ and was prescribed propylthiouracil. During the long-term follow-up, the total insulin and IAB levels gradually declined. There was no other episode of hypoglycemia. Therefore, in adolescents with Graves' disease receiving antithyroid treatment with MTZ who experience hypoglycemia, the IAB levels should be assessed to exclude or confirm IAS as the underlying cause.


How does grazing relate to body mass index, self-compassion, mindfulness and mindful eating in a student population?
Contemporary research investigating obesity has focused on grazing (i.e. an uncontrolled and repetitive consumption of small amounts of food). Meanwhile, constructs such as mindfulness, mindful eating and self-compassion have received much attention in assisting individuals with eating behaviours and weight regulation. The association between those constructs and grazing, however, has not been explored. In a cross-sectional study, university students (n = 261) were recruited to explore the relationship of mindfulness, mindful eating and self-compassion with current weight and grazing. Results indicated that all constructs were negatively related to grazing, but only mindful eating related negatively to current weight. In addition, mindful eating mediated the relationship between grazing and current weight. Possible explanations and future directions are discussed further with an emphasis on the need for more empirical work.


Selective Oxidative Phenol Coupling by Iron Catalysis.
The iron-catalyzed oxidative coupling of phenols has emerged as a powerful method for preparing complex phenolic frameworks from simple and readily available compounds. This synopsis describes the selectivity challenges inherent in oxidative coupling reactions while at the same time presents our mechanistic-driven strategy employed to confront them.


The role of disease-specific infectivity and number of disease exposures on long-term effectiveness of the latex condom.
Condom use is a primary prevention strategy for sexually transmitted infections (STIs). Consistent condom use substantially reduces the risk of HIV infection. Similar levels of effectiveness for reducing the risk of other STIs have not been established. Differences in disease-specific infectivity and the number of exposures to an infected partner may explain differences in condom effectiveness. The goal was to examine the impact of differing infectivities and increasing numbers of exposures on theoretical condom effectiveness. Mathematical modeling using estimated disease-specific infectivities and condom failure rates. Condom effectiveness decreases as disease-specific infectivity and the number of exposures to infection risk increase. Condom effectiveness for decreasing STI risk is influenced by disease infectivity and the number of exposures. Generalizations from studies of relatively uninfectious STIs to highly infectious STIs or from short-term studies to longer-term situations will overestimate condom effectiveness.


True hermaphroditism with seminoma: A case report.
The aim of the present study was to discuss the diagnosis and treatment of a patient with true hermaphroditism complicated by seminoma. The patient was a 35-year-old man who was admitted to the Peking University Shenzhen Hospital with a retractable mass in the left inguinal region for 20 years. A computed tomography examination revealed right cryptorchidism. The postoperative pathology suggested true hermaphroditism with a seminoma. The results of immunohistochemical examination were as follows: Sal-like protein 4+ (partially weak); octamer-binding transcription factor 4+ (partially weak); CD117+; cytokeratin+; CD30-, α-fetoprotein-, inhibin-α-. The karyotype was 46, XY. Adult true hermaphroditism combined with seminoma is rare in clinical practice. Combined histopathological analysis, immunophenotype detection and karyotype analysis are of great value in the diagnosis and differential diagnosis. Early intervention and combined surgery with radiotherapy and chemotherapy can significantly improve the prognosis of such patients.


Criminal thinking and psychosocial characteristics among young adults entering residential substance use treatment.
Background and aim: Young adults with substance use (SU) problems face a high risk of co-occurring problems, including criminality. The aim of the present study was to assess the psychosocial characteristics, SU problems, and criminal thinking young adults entering SU treatment have, and whether the SU characteristics, sex and age are associated with criminal thinking scores. Methods: The sample was 407 young adults aged 16-29 years who underwent an entry assessment between January 2011 and December 2016 at a residential SU treatment institution in Norway. All study data were extracted from electronic health records, including survey information from the Achenbach System of Empirically Based Assessment and the Psychological Inventory of Criminal Thinking Styles. Results: In the present sample, severe SU, high rates of psychosocial problems, and criminal thinking were reported. Almost three-quarters (72.67%) of young adults reported high levels of criminal thinking (≥60). However, male participants were more likely to report high levels of criminal thinking compared to female participants (p=0.031). In bivariate regression models, only sex and having stimulants/opioids as primary drug were associated with mean levels of criminal thinking. The same was true in the multiple regression model. Conclusion: Young adults in residential SU treatment are a multi-problem high-risk/high-need group of people. Due to the elevated levels of criminal thinking, we recommend that young adults in SU treatment should be screened for criminogenic treatment needs, such as criminal thinking, regardless of justice involvement.


Performance of disc diffusion, MIC gradient tests and Vitek 2 for ceftolozane/tazobactam and ceftazidime/avibactam susceptibility testing of Pseudomonas aeruginosa.
To assess performance of disc diffusion, gradient tests and Vitek 2 system to determine the susceptibility of clinical Pseudomonas aeruginosa strains to ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA). Two-hundred non-duplicate P. aeruginosa strains isolated by 47 French medical laboratories were selected to cover a wide range of C/T and CZA MICs. Performance of C/T disc (30/10 μg, Bio-Rad), CZA discs (10/4 μg) (Thermo Fisher and Bio-Rad), C/T and CZA gradient tests (Etest, BioMérieux; MIC Test Strip, Liofilchem), and AST-XN12 card of Vitek 2 system (BioMérieux) were compared with a broth microdilution (BMD) method (Thermo Fisher). MIC and disc results were interpreted using current EUCAST breakpoints. Twenty percent and 17% of strains were resistant to C/T and CZA, respectively. All the methods tested satisfactorily determined the susceptibility of P. aeruginosa to C/T [Category Agreement (CA) ≥95%] except the disc diffusion method. Because of the high rates of Major Errors (MEs) (12.5%), this latter method tends to overestimate the resistance. For CZA, only the gradient tests yielded more than 90% of CA. The Vitek 2 system and disc diffusion misclassified 18.1%, 10.1% (disc Bio-Rad) and 11.9% (disc Thermo Fisher) of susceptible strains, respectively. The gradient tests (MIC Test Strip and Etest) and Vitek 2 card XN12 performed the best to determine the susceptibility of P. aeruginosa to C/T, whereas gradient tests were an acceptable alternative to BMD to assess CZA susceptibility.