High-sucrose diets in male rats disrupt aspects of decision making tasks, motivation and spatial memory, but not impulsivity measured by operant delay-discounting.
Excessive consumption of sugar sweetened drinks is proposed to produce functional changes in the hippocampus and prefrontal cortex, leading to perturbations in behavioural control. Impairments in behavioural control have been observed in obese people on tasks that involve making choices, including delay-discounting, indicative of increased impulsivity. In this study we examined the impact of 2h daily access to 10% sucrose (or no sucrose in controls) in young male rats on behavioural tasks reliant on hippocampal function including delay-discounting, T-maze forced choice alternation and place recognition memory, as well as progressive ratio to measure motivation. We observed deficits in place recognition memory and T-maze forced choice alternation, indicative of hippocampal deficits in rats with a history of sucrose consumption. Moreover, rats with a history of sucrose consumption were less motivated to lever press for rewards on a progressive ratio schedule. However, rats with a history of sucrose consumption performed equally to control animals during the delay-discounting task, suggesting that they discounted for reward size over a delay in a manner comparable to control animals. These findings indicate that high-sucrose diets impact on spatial and working memory processes, but do not induce impulsive-like choice behaviours in rats, suggesting that unhealthy diet choices may not influence this aspect of decision-making behaviour.


Actinomyces israelii in radicular cysts: a molecular study.
To investigate whether the microscopic filamentous aggregates observed in radicular cysts are associated with the molecular identification of Actinomyces israelii. Moreover, to verify whether this bacterium can be detected in radicular cyst specimens not presenting aggregates. Microscopic colonies suggestive of Actinomyces were found in 8 out of 279 radicular cyst samples (case group). The case and control groups (n = 12; samples without filamentous colonies) were submitted to the semi-nested polymerase chain reaction to test the presence of A israelii. DNA sequencing was performed to validate polymerase chain reaction results. Two and 3 samples in the case and control groups, respectively, did not present a functional genomic DNA template and were excluded from the study. A israelii was identified in all samples of the case group and in 3 out of 9 samples of the control group. Although A israelii is more commonly identified in radicular cysts presenting filamentous aggregates, it also appears to be detected in radicular cysts without this microscopic finding.


Epigenetics in developmental defects of enamel: A scoping review.
The significant role of epigenetics has been revealed in normal enamel formation process and occurrence of developmental defects. This presented literature is aiming at summarizing the regulatory function of epigenetics in physiological amelogenesis process and reviewing the epigenetic mechanisms in occurrence of developmental defects of enamel (DDE), so as to provide biological foundation evidence to support early predication and clinical management of DDE. An extensive literature review was conducted using electronic databases MEDLINE (through PubMed), Web of Science and EMBASE up to November 30, 2022. Studies about epigenetic effects on enamel tissue or cells associated with amelogenesis, including in vivo studies using human or animal models, and in vitro studies, are selected. A total of 22 studies were included. Epigenetic factors or effects specifically activate or silence certain genes, which may regulate related biological activities including cell proliferation, cell differentiation, enamel secretion, and mineralization during the process of amelogenesis. Once the status of epigenetic modification is altered, the quantity and quality of enamel may both be disturbed, which can finally result in DDE. Epigenetics plays a noteworthy role of regulating the amelogenesis process and DDE potentially by altering the expression levels of genes related to enamel formation, providing a new perspective of early predication and clinical management of DDE.


Cell-type-specific modulation of Hox gene expression by members of the TGF-beta superfamily: a comparison between human osteosarcoma and neuroblastoma cell lines.
Homeobox gene expression in osteoblast-like cells was investigated using the polymerase chain reaction (PCR). A total of 13 homeobox genes was detected in U-2 OS (human osteosarcoma) and MC3T3-E1 (mouse osteoblast) cells by sequencing cloned PCR products. Using specific primers, a different pattern of Hox gene expression was shown for the neuroblastoma cell line SK-N-SH relative to U-2 OS and MC3T3-E1. Additionally, we showed that expression of HOXC6 in U-2 OS and SK-N-SH was differentially regulated by rhBMP-2, TGF-beta and activin-A. This suggests that specific Hox genes may be target genes for TGF-beta superfamily members, and allows us to further understand the complex functions of these growth factors and how they relate to growth and development.


The results of surgery for nail dystrophy of the hallux in children.
The efficacy of surgery for nail dystrophy of the hallux has been evaluated in 52 children studied retrospectively. 69 primary procedures were carried out with an overall symptomatic recurrence rate of 40%. When used as a primary procedure, avulsion alone had a symptomatic recurrence rate of 54% and Zadik 's procedure 29%. When avulsion was repeated, the recurrence rate rose to 100%. Avulsion alone cannot be recommended, but if surgery is contemplated Zadik 's procedure is the most effective.


Plasma lipids and lipoproteins during first trimester in pregnant Nigerian women: Ilorin experience.
Thirty-two pregnant women in their first trimester with a mean age of 29.5 years, 32 age matched non-pregnant controls were included in this study. They were bled after 14-hour fasting. This study was between October 2000 and October 2001. Plasma total cholesterol, triglyceride and HDL- cholesterol were assayed. LDL-cholesterol was obtained through Frieldwald formula average as mean were calculated using Epi info version 6.0 and level of significant difference decided at p<0. 05. The mean age of the subjects was 9.5 years. Compared to the concentration in non-pregnant women [controls] the plasma level of total cholesterol and HDL-cholesterol were found to be significantly lower p<0.05. However the levels of plasma triglyceride and LDL-cholesterol were found to be significantly higher in the pregnant women than the control group [p<0.05]. This study revealed that the level of total plasma cholesterol is low in middle part of first trimester. We therefore suggest that in interpreting the result of total cholesterol in first trimester the gestation age should be put into consideration.


Cobalt(III) Chaperone Complexes of Curcumin: Photoreduction, Cellular Accumulation and Light-Selective Toxicity towards Tumour Cells.
Light-activated prodrugs offer the potential for highly selective tumour targeting. However, the application of many photoactivated chemotherapeutics is limited by a requirement for oxygen, or for short activation wavelengths that can damage surrounding tissue. Herein, we present a series of cobalt(III)-curcumin prodrugs that can be activated by visible light under both oxygenated and hypoxic conditions. Furthermore, the photoproduct can be controlled by the activation wavelength: green light yields free curcumin, whereas blue light induces photolysis of curcumin to a phototoxic product. Confocal fluorescence microscopy and phototocytotoxicity studies in DLD-1 and MCF-7 tumour cells demonstrated that the cobalt(III) prodrugs are nontoxic in the dark but accumulate in significant concentrations in the cell membrane. When cells were treated with light for 15 min, the cytotoxicity of the cobalt complexes increased by up to 20-fold, whereas free curcumin exhibited only a two-fold increase in cytotoxicity. The nature of the ancillary ligand and cobalt reduction potential were found to strongly influence the stability and biological activity of the series.


Monitoring of acetyl salicylic acid-induced platelet inhibition with impedance aggregometry in children with systemic-to-pulmonary shunts.
Shunt thrombosis after implantation of systemic-to-pulmonary shunts in paediatric patients is common. Acetyl salicylic acid is used for anti-thrombotic treatment; however, the effect is rarely monitored, although it is known that the response varies. The aim was to determine the effects of acetyl salicylic acid medication on platelet aggregation in children with systemic-to-pulmonary shunts. A total of 14 children – median age 12 days; ranging from 3 to 100 days – were included in a prospective observational longitudinal study. All children were treated with oral acetyl salicylic acid (3–5 milligrams per kilogram once daily) after shunt implantation. Acetyl salicylic acid-dependent platelet aggregation in whole blood was analysed with impedance aggregometry (Multiplate®) after addition of arachidonic acid. Analyses were carried out before the primary operation, before and 5 and 24 hours after the first acetyl salicylic acid dose, and after 3–6 months of treatment. The therapeutic range for acetyl salicylic acid was defined as a test result less than 60 units. Acetyl salicylic acid reduced the arachidonic acid-induced platelet aggregation in all but one patient. Of the patients, 93% were in the therapeutic range 5 hours after acetyl salicylic acid intake, 86% were in the range after 24 hours, and 64% after 3–6 months. Acetyl salicylic acid reduces platelet aggregation after shunt implantation in paediatric patients, but a considerable percentage of the children are outside the therapeutic range. Monitoring of platelet aggregation has the potential to improve anti-platelet treatment after shunt implantation by identifying children with impaired acetyl salicylic acid response.


Assessment of perfluoroalkyl substances in food items at global scale.
This study assessed the levels of 21 perfluoroalkyl substances (PFASs) in 283 food items (38 from Brazil, 35 from Saudi Arabia, 174 from Spain and 36 from Serbia) among the most widely consumed foodstuffs in these geographical areas. These countries were chosen as representatives of the diet in South America, Western Asia, Mediterranean countries and South-Eastern Europe. The analysis of foodstuffs was carried out by turbulent flow chromatography (TFC) combined with liquid chromatography with triple quadrupole mass spectrometry (LC-QqQ-MS) using electrospray ionization (ESI) in negative mode. The analytical method was validated for the analysis of different foodstuff classes (cereals, fish, fruit, milk, ready-to-eat foods, oil and meat). The analytical parameters of the method fulfill the requirements specified in the Commission Recommendation 2010/161/EU. Recovery rates were in the range between 70% and 120%. For all the selected matrices, the method limits of detection (MLOD) and the method limits of quantification (MLOQ) were in the range of 5 to 650 pg/g and 17 to 2000 pg/g, respectively. In general trends, the concentrations of PFASs were in the pg/g or pg/mL levels. The more frequently detected compounds were perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorobutanoic acid (PFBA). The prevalence of the eight-carbon chain compounds in biota indicates the high stability and bioaccumulation potential of these compounds. But, at the same time, the high frequency of the shorter chain compounds is also an indication of the use of replacement compounds in the new fluorinated materials. When comparing the compounds profile and their relative abundances in the samples from diverse origin, differences were identified. However, in absolute amounts of total PFASs no large differences were found between the studied countries. Fish and seafood were identified as the major PFASs contributors to the diet in all the countries. The total sum of PFASs in fresh fish and seafood was in the range from the MLOQ to 28ng/g ww. According to the FAO-WHO diets composition, the daily intake (DI) of PFASs was calculated for various age and gender groups in the different diets. The total PFASs food intake was estimated to be between 2300 and 3800 ng /person per day for the different diets. Finally, the risk intake (RI) was calculated for selected relevant compounds. The results have indicated that by far in no case the tolerable daily intake (TDI) (150, 1500, 50,000, 1,000,000, 150, 1500 ng/kg body weight, for perfluorohexanesulfonate (PFHxS), fluorotelomer alcohol (FTOH), perfluorobutanesulfonic acid (PFBS), perfluorobutanoic acid (PFBA), PFOS and PFOA, respectively) was exceeded.


Information resource preferences by general pediatricians in office settings: a qualitative study.
Information needs and resource preferences of office-based general pediatricians have not been well characterized. Data collected from a sample of twenty office-based urban/suburban general pediatricians consisted of: (a) a demographic survey about participants' practice and computer use, (b) semi-structured interviews on their use of different types of information resources and (c) semi-structured interviews on perceptions of information needs and resource preferences in response to clinical vignettes representing cases in Genetics and Infectious Diseases. Content analysis of interviews provided participants' perceived use of resources and their perceived questions and preferred resources in response to vignettes. Participants' average time in practice was 15.4 years (2-28 years). All had in-office online access. Participants identified specialist/generalist colleagues, general/specialty pediatric texts, drug formularies, federal government/professional organization Websites and medical portals (when available) as preferred information sources. They did not identify decision-making texts, evidence-based reviews, journal abstracts, medical librarians or consumer health information for routine office use.In response to clinical vignettes in Genetics and Infectious Diseases, participants identified Question Types about patient-specific (diagnosis, history and findings) and general medical (diagnostic, therapeutic and referral guidelines) information. They identified specialists and specialty textbooks, history and physical examination, colleagues and general pediatric textbooks, and federal and professional organizational Websites as information sources. Participants with access to portals identified them as information resources in lieu of texts. For Genetics vignettes, participants identified questions about prenatal history, disease etiology and treatment guidelines. For Genetics vignettes, they identified patient history, specialists, general pediatric texts, Web search engines and colleagues as information sources. For Infectious Diseases (ID) vignettes, participants identified questions about patients' clinical status at presentation and questions about disease classification, diagnosis/therapy/referral guidelines and sources of patient education. For ID vignettes, they identified history, laboratory results, colleagues, specialists and personal experience as information sources. Content analysis of office-based general pediatricians' responses to clinical vignettes provided a qualitative description of their perceptions of information needs and preferences for information resource for cases in Genetics and Infectious Diseases. This approach may provide complementary information for discovering practitioner's information needs and resource preferences in different contexts.


Local IL-21 promotes the therapeutic activity of effector T cells by decreasing regulatory T cells within the tumor microenvironment.
The eradication of tumors by the immune system depends on the generation of antigen-specific T cells which can migrate to sites of tumor growth and maintain their effector functions despite local tumor-derived T-cell inhibitory factors. Interleukin-21 (IL-21) is an IL-2-related cytokine that has shown limited evidence of antitumor activity in murine models and early phase clinical trials. Effect of local IL-21 on T-cell responses within the tumor microenvironment, however, has not been extensively evaluated. Thus, we developed a stably transfected IL-21-secreting B16 melanoma cell line to test the effects of local IL-21 on endogenous and adoptively transferred T-cell responses. Tumors expressing IL-21 exhibited delayed growth in vivo, which was associated with an increase in activated systemic effector and memory CD8(+) T-cell responses. Local IL-21 also enhanced the therapeutic effects of adoptively transferred gp100-specific T cells and was synergistic with IL-2. The effect was also associated with an increased proliferation of local CD8(+) T cells and decreased accumulation of regulatory CD4(+)FOXP3(+) T cells within the tumor microenvironment. These data suggest that local IL-21 enhances endogenous and adoptively transferred T-cell immunity through increased effector CD8(+) T cells and decreased CD4(+) regulatory T cells in the tumor microenvironment.


Dynamic variability of binding of antiarrhythmic drugs during the evolution of acute myocardial infarction.
We tested the hypothesis that the changes in free fatty acid and alpha 1-glycoprotein concentrations, which occur during acute myocardial infarction, exert asynchronous and opposing influences on the serum protein binding of selected drugs. Free drug fractions of two antiarrhythmic agents with contrasting binding characteristics, quinidine and procainamide, were related to free fatty acid and alpha 1-glycoprotein concentrations on days 1 through 5 and 10 in 20 patients with acute myocardial infarction. The mean free quinidine fraction was elevated on day 1 (9.0 +/- 4.4% vs 6.7 +/- 2.7% in patients with stable heart disease; p less than .05) and fell progressively to day 10 (4.0 +/- 2.8%; p less than .0002) as free fatty acid concentration decreased (day 1 = 464 +/- 272 meq/liter; day 10 = 264 +/- 155 meq/liter; p less than .01) and alpha 1-glycoprotein concentration increased (day 1 = 98 +/- 31 mg/dl; day 10 = 141 +/- 47 mg/dl; p less than .02). Multiple stepwise regression showed a major influence of changing alpha 1-glycoprotein concentration on the observed sequential changes in the free quinidine fraction (p less than .005). In contrast, no serial changes in procainamide binding were noted. In conclusion, metabolic changes during the course of acute myocardial infarction sequentially alter free quinidine fraction and, consequently, may influence pharmacodynamics.


Educating the cancer patient about the immunotherapy toxicity: a descriptive observational study.
Immunotherapy can cause immune-related adverse events. Recognizing and communicating these symptoms is important for the patient to allow nurses to manage them promptly, avoiding complications or interruptions in therapy. We conducted an observational study with the objective of creating a readable tool to be shared with patients to provide information on immune-related adverse events and provide clinical guidance to prevent and manage symptoms. Secondary objective was to determine the acceptability of the tool through a questionnaire developed ad hoc. For each patient, data were collected such as: sex, age, educational qualification, marital status, area of residence, diagnosis, comorbidities, therapy, performance status. The information tool and a questionnaire were administered with the aim of evaluating its acceptability and feasibility. 35 patients were enrolled (mean age 65 years, standard deviation 10.7). The drugs used are: Pembrolizumab, Nivolumab, Atezolizumab, Durvalumab. A preliminary analysis of the data revealed a poor knowledge of immune-related adverse events (skin rash, thyroid disorders, pneumonia, gastrointestinal disorders, fatigue). All patients find the educational tool useful and easy to understand for recognizing and managing symptoms of therapy. The format of the tool was also appreciated. Patient education is of fundamental importance to ensure early identification of immune-related adverse events, to avoid severe grades of toxicity and therapy interruptions, also causing a poor patient quality of life. The nurse has a fundamental role in educating the patient about possible immune related adverse events and training courses are also needed in collaboration with oncologists.


Clinical Monitoring of Tooth Wear Progression in Patients over a Period of One Year Using CAD/CAM.
The aim of this study was to clinically monitor the progression of tooth wear over a period of 1 year in a cohort of referred tooth wear patients through the use of a computer-aided design/computer-assisted manufacture (CAD/CAM) scanner and a standardized scanning/assessment methodology. Polyether impressions were made of 11 participants (130 teeth) at baseline and at 1 year. Impressions were poured in type IV dental stone and the anterior teeth were 3D scanned. A surface-matching software was used to compare 1-year and baseline scans and identify any dimensional differences. Parafunctional habits were reported by all patients. All participants exhibited tooth wear ≥ 140 μm in depth and extending to ≥ 280 μm in at least one tooth. Maxillary central incisors were the most commonly and severely affected teeth. The ability of the developed CAD/CAM scanning methodology in clinical monitoring of tooth wear was demonstrated. Further research is needed to assess its practicality in large-scale epidemiologic tooth wear studies.


Anesthetic considerations in patients with gas gangrene.
Anesthesia for a patient with gas gangrene presents a challenge for the anesthesiologist, since it is an uncommon disease requiring emergency treatment. The authors, faced with such a challenge and finding little guidance in the literature, have proposed modalities of anesthetic management based on pathophysiology, symptomatology, and the reported experience of others. In addition to choice of anesthetic agents, problems reviewed include shock, hypovolemia, tachycardia, fever, anemia, renal dysfunction, pulmonary insufficiency, and contamination. Factors relating to anesthesia during hyperbaric-O2 therapy are also reviewed.


Emission of volatile organic compounds and production of secondary organic aerosol from stir-frying spices.
Cooking is an important source of volatile organic compounds (VOCs) and a potential source of secondary organic aerosol (SOA) both indoors and outdoors. In this study, VOC emissions from heating corn oil and stir-frying spices (i.e. garlic, ginger, myrcia and zanthoxylum piperitum (Sichuan pepper)) were characterized using an on-line membrane inlet vacuum ultraviolet single-photon ionization time-of-flight mass spectrometer (VUV-SPI-TOFMS). VOC emissions from heating corn oil were dominated by aldehydes, which were enhanced by factors of one order of magnitude when stir-frying spices. Stir-frying any of the spices studied generated large amounts of methylpyrrole (m/z 81). In addition, stir-frying garlic produced abundant dihydrohydroxymaltol (m/z 144) and diallyldisulfide (DADS) (m/z 146), while stir-frying ginger, myrcia and zanthoxylum piperitum produced abundant monoterpenes (m/z 136) and terpenoids (m/z 152, 154). SOA formed from emissions of stir-frying spices through reactions with excess ozone in a flow reactor as well as primary organic aerosol (POA) emissions were characterized using a scanning mobility particle sizer (SMPS) and a high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS). Stir-frying garlic and ginger generated similar POA concentrations to those from heating corn oil while stir-frying myrcia and zanthoxylum piperitum generated double the amount of emissions. No SOA was observed from stir-frying garlic and ginger. The rates of SOA production from stir-frying myrcia and zanthoxylum piperitum were 1.8μgmin-1gspice-1 and 8.7μgmin-1gspice-1, equivalent to 13.4% and 53.1% of their own POA emission rates, respectively. Therefore, the contribution of stir-frying spices to ambient organic aerosol levels is likely dominated by POA. The rates of total terpene emission from stir-frying myrcia and zanthoxylum piperitum were estimated to be 5.1μgmin-1gspice-1 and 24.9μgmin-1gspice-1, respectively. Our results suggest that stir-frying spices could be an important source of terpenes in indoor environments in Hong Kong, at least during cooking.


Changes to daily feed intake during the laying period alters embryonic MSTN and MYOG gene expression in genetically fat and lean lines of chickens.
1. Broiler breeders are unable to self-regulate feed intake to a level that permits reproductive function and restricted feeding is normal for broiler parent stock. The aim of this study was to determine whether myostatin (MSTN) and myogenin (MYOG) mRNA expression could be altered in relation to differences in body composition of the embryos and the hen's diet. 2. A 2 × 2 factorial experiment was conducted with two dietary intake levels (100% and 75% of nutrition recommendation) and two broiler genotypes (Fat line and Lean line). Hens (384 of each line) were randomly divided at 23 weeks of age into 4 treatments, with each treatment represented by 12 replicates of 16 birds each. The experiment started when the rate of lay reached 5% and continued until 54 weeks of age. 3. There were significant effects of line and dietary intake, and interactions between them on MSTN and MYOG mRNA expression levels in embryonic tissues. The trend in MSTN mRNA expression level over the embryonic period was similar between lines. Low daily feed intake did not alter the trend in MSTN mRNA expression levels in either line, but significantly changed the peak values. MYOG mRNA expression varied by line and over time, with a delay in the Lean line. Low daily feed intake influenced the trend in MYOG mRNA expression levels in both lines and delayed its onset.


Tissue pathology in undergraduate medical education: atrophy or evolution?
Changes are occurring in undergraduate medical curricula and there is limited published information about how contemporary tissue pathology is taught. The aim of this study was to collect information on this topic and to invite expert opinion about best teaching practice. A postal questionnaire survey of medical schools in the UK was performed, with a response rate of 23/28 schools (82%). The two most striking findings were the variation in teaching and learning strategies between schools and the spirit of the respondents, some relishing the challenges associated with reorganization and some thoroughly demoralized. The main concerns about pathology teaching were a feeling of lack of ownership of the content taught, an overall lack of visibility of tissue pathology in teaching and assessment, and staff shortages. Respondents valued the autopsy as an educational tool but were finding it increasingly difficult to provide. On the other hand, key opportunities for pathology teaching were highlighted through the questionnaire. The potential for developments in information technology and the possibility of creating national forums to develop core curricula and generate e-resources was recognized. The findings of this study will provide a milestone against which future change in pathology education can be measured.


Synthesis and Screening of Phase Change Chalcogenide Thin Film Materials for Data Storage.
A combinatorial synthetic methodology based on evaporation sources under an ultrahigh vacuum has been used to directly synthesize compositional gradient thin film libraries of the amorphous phases of GeSbTe alloys at room temperature over a wide compositional range. An optical screen is described that allows rapid parallel mapping of the amorphous-to-crystalline phase transition temperature and optical contrast associated with the phase change on such libraries. The results are shown to be consistent with the literature for compositions where published data are available along the Sb2Te3-GeTe tie line. The results reveal a minimum in the crystallization temperature along the Sb2Te3-Ge2Te3 tie line, and the method is able to resolve subsequent cubic-to-hexagonal phase transitions in the GST crystalline phase. HT-XRD has been used to map the phases at sequentially higher temperatures, and the results are reconciled with the literature and trends in crystallization temperatures. The results clearly delineate compositions that crystallize to pure GST phases and those that cocrystallize Te. High-throughput measurement of the resistivity of the amorphous and crystalline phases has allowed the compositional and structural correlation of the resistivity contrast associated with the amorphous-to-crystalline transition, which range from 5-to-8 orders of magnitude for the compositions investigated. The results are discussed in terms of the compromises in the selection of these materials for phase change memory applications and the potential for further exploration through more detailed secondary screening of doped GST or similar classes of phase change materials designed for the demands of future memory devices.


Imaging of electrostatic field vector distribution.
This paper reports on the visualization of a two-dimensional distribution of electrostatic field vectors around an electrified object using the electric field imager (EFIM) device. The EFIM device is made of a virtually connected pair of plate electrodes in parallel and in proximity, between which an electronic circuit for detection and optical indication is embedded. The EFIM device is not only accurately sensitive to the electrostatic field but also possessed of agility and mobility together with directivity and noninvasiveness. It was successfully demonstrated that electrostatic field vectors were visualized quantitatively, and their spatial distributions were mapped in combination with rather simple, mobile, and low-cost equipment. The advantages and disadvantages of the EFIM visualization scheme are discussed together with the future prospect of the EFIM device.


Dual sensitivity of sarcoplasmic/endoplasmic Ca2+-ATPase to cytosolic and endoplasmic reticulum Ca2+ as a mechanism of modulating cytosolic Ca2+ oscillations.
The effects of ER (endoplasmic reticulum) Ca2+ on cytosolic Ca2+ oscillations in pancreatic acinar cells were investigated using mathematical models of the Ca2+ oscillations. We first examined the mathematical model of SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) to reproduce the highly co-operative inhibitory effect of Ca2+ in the ER lumen on ER Ca2+ uptake in the acinar cells. The model predicts that luminal Ca2+ would most probably inhibit the conversion of the conformation state with luminal Ca2+-binding sites (E2) into the conformation state with cytoplasmic Ca2+-binding sites (E1). The SERCA model derived from this prediction showed dose-response relationships to cytosolic and luminal Ca2+ concentrations that were consistent with the experimental data from the acinar cells. According to a mathematical model of cytosolic Ca2+ oscillations based on the modified SERCA model, a small decrease in the concentration of endoplasmic reticulum Ca2+ (approx. 20% of the total) was sufficient to abolish the oscillations. When a single type of IP3R (IP3 receptor) was included in the model, store depletion decreased the spike frequency. However, the frequency became less sensitive to store depletion when we added another type of IP3R with higher sensitivity to the concentration of free Ca2+ in the cytosol. Bifurcation analysis of the mathematical model showed that the loss of Ca2+ from the ER lumen decreased the sensitivity of cytosolic Ca2+ oscillations to IP3 [Ins(1,4,5)P3]. The addition of a high-affinity IP3R did not alter this property, but significantly decreased the sensitivity of the spike frequency to IP3. Our mathematical model demonstrates how luminal Ca2+, through its effect on Ca2+ uptake, can control cytosolic Ca2+ oscillations.


Detection of receptors for immunoglobulin on human placenta by EA rosette formation.
Direct evidence for the existence of Fc receptors on the surface of first trimester and term human placental cells has been obtained by the use of an antibody-coated red cell (EA) rosette assay. The modification of a Ficoll density gradient separation procedure for placental cell population in conjunction with dye uptake experiments, cytocentrifuge preparations and cytological analysis has enabled an identification of the rosette-forming cells in the mature placenta as predominantly, if not entirely, syncytiotrophoblastic. The significance of these findings, together with those demonstrating the presence of cell-surface Fc receptors on the chorionic membrane, are considered in relation to the transmission of immunoglobulin from mother to foetus and to the protection of the foetus as an intra-uterine allograft.


How prevention of violence in childhood builds healthier economies and smarter children in the Asia and Pacific region.
Investments in preventing violence against children in the Asia and Pacific region will bring important social and economic returns that contribute to building the region's 'cognitive capital'. An analysis of burden of violence research in the region is presented to identify the impacts of violence and to demonstrate these returns. Violence is an everyday experience in the lives of many children in the Asia-Pacific, and the toxic stress associated with such routine forms of violence may permanently impact the architecture and chemistry of the developing brain. This can undermine learning and affect behavioural, social and emotional functioning as children grow into adulthood. Given the hundreds of millions of children affected by violence in the region each year, its cumulative impact translates into the annual loss of hundreds of billions of dollars-or about 2% of gross domestic product of the Asia and Pacific region. Violence prevention can affect positively on health and productivity, reduce expenditure on crisis response, improve children's developmental and educational outcomes, and prevent crime. The sustainable development goals and the emerging global consensus on effective prevention strategies constitute a powerful new agenda to end violence against children, and there are critical steps that governments can take to accelerate action.


Task Performance Modulates Functional Connectivity Involving the Dorsolateral Prefrontal Cortex in Patients with Schizophrenia.
Previous studies have suggested that patients with schizophrenia and healthy controls exhibit differential activation of and connectivity involving the dorsolateral prefrontal cortex (DLPFC) during working memory tasks, though their findings remain inconsistent. The functional integration perspective further suggests that working memory performance also modulates differences in functional interactions of the DLPFC between patients and controls. To explore this possibility, 45 healthy controls and 45 patients with schizophrenia were recruited to perform a 2-back task during functional magnetic resonance imaging (fMRI). Each group was further divided into two subgroups based on task performance to examine the modulatory effect of performance on functional interactions of the DLPFC, as measured via psychophysiological interaction (PPI) analyses. We observed that, in patients with schizophrenia who exhibited impaired working memory capacity and decreased brain activation/deactivation, functional interactions between the right/left DLPFC and angular cortex were decreased relative to those of healthy controls. Furthermore, we observed an interaction effect of working memory performance and diagnosis on functional connectivity between the right/left DLPFC seed region and posterior regions such as the angular cortex, fusiform gyrus, and middle occipital gyrus. This interaction effect was mainly driven by the negative correlation between functional connectivity and performance in healthy controls, and by the positive correlation in patients with schizophrenia. These results demonstrate the effects of inter-individual differences in working memory performance on functional interactions between the DLPFC and posterior regions in patients with schizophrenia as well as healthy controls, which may shed new light on the neural basis of working memory.


Monte Carlo simulations of polyampholyte-polyelectrolyte complexes: effect of charge sequence and strength of electrostatic interactions.
We present the results of Monte Carlo simulations of complexation between polyampholyte and polyelectrolyte chains. Polymers are modeled as bead-spring chains of charged Lennard-Jones particles each consisting of 32 monomers. Formation of a polyampholyte-polyelectrolyte complex is driven by polarization-induced attractive interactions. The complex is usually formed at the end of the polyelectrolyte with the polyampholyte chain elongated and aligned along the polyelectrolyte backbone. This complex structure between the polarized polyampholyte chain and the polyelectrolyte leads to maximization of the attractive and minimization of the repulsive electrostatic interactions. The size of a polyampholyte in a complex is usually larger than that of an isolated polyampholyte chain. We also observed that initially collapsed polyampholytes undergo a coil-globule transition by forming a complex. The structure of a polyampholyte-polyelectrolyte complex was analyzed by tail and loop distribution functions. We have found that the number of loops increases while their sizes decrease with the strength of the electrostatic interactions. Polyampholytes with random charge sequence form stronger complexes with polyelectrolytes than those with alternating charge sequence. Polyampholytes with long blocky sequences form a double helix with a polyelectrolyte at sufficiently large values of the Bjerrum length.


Spectral analysis of full field digital mammography data.
The spectral content of mammograms acquired from using a full field digital mammography (FFDM) system are analyzed. Fourier methods are used to show that the FFDM image power spectra obey an inverse power law; in an average sense, the images may be considered as 1/f fields. Two data representations are analyzed and compared (1) the raw data, and (2) the logarithm of the raw data. Two methods are employed to analyze the power spectra (1) a technique based on integrating the Fourier plane with octave ring sectioning developed previously, and (2) an approach based on integrating the Fourier plane using rings of constant width developed for this work. Both methods allow theoretical modeling. Numerical analysis indicates that the effects due to the transformation influence the power spectra measurements in a statistically significant manner in the high frequency range. However, this effect has little influence on the inverse power law estimation for a given image regardless of the data representation or the theoretical analysis approach. The analysis is presented from two points of view (1) each image is treated independently with the results presented as distributions, and (2) for a given representation, the entire image collection is treated as an ensemble with the results presented as expected values. In general, the constant ring width analysis forms the foundation for a spectral comparison method for finding spectral differences, from an image distribution sense, after applying a nonlinear transformation to the data. The work also shows that power law estimation may be influenced due to the presence of noise in the higher frequency range, which is consistent with the known attributes of the detector efficiency. The spectral modeling and inverse power law determinations obtained here are in agreement with that obtained from the analysis of digitized film-screen images presented previously. The form of the power spectrum for a given image is approximately l/f2beta with beta approximately 1.4-1.5.


[Initial studies of 3-dimensional imaging using ultrasound].
In the study reported here three-dimensional sonographic imaging of organs was achieved for the first time. To make this possible it was first necessary to ensure, by appropriate guidance of the probe, that the sequence of sonographic sections was coordinated in their spatial arrangement. This was accomplished by constructing a probe guide with which parallel sonographic sections could be demonstrated. The distance between these sections was known, so that with the aid of suitable computer programs three-dimensional reconstruction of a kidney examined in a water bath was possible. Since, however, due to the uneven surface of the body, it will hardly be possible to obtain parallel sonographic sections of an organ, a new solution had to be found to ensure the necessary coordinated sequence of sections. The solution lay in rotating the probe. A further device was constructed in which the probe could be rotated farther, by known angles, from section to section. The pivotal point was at the center of the probe tip. The computer knew the angular distance between these sections and reconstruction to a three-dimensional image was therefore possible. Prior the three-dimensional reconstruction the ultrasonographic sections had to be contoured, since only the surface of the organ was available for three-dimensional image construction. Three-dimensional imaging of an organ can be achieved on the one hand by binary representation and on the other with a continuous organ surface. The advantage of binary representation is that the original sonographic data are incorporated in the image-producing process without any computer manipulation; with a continuous surface the distance between the individual sections has to be interpolated.(ABSTRACT TRUNCATED AT 250 WORDS)


Improvement of xylanase production by Aspergillus niger XY-1 using response surface methodology for optimizing the medium composition.
To study the optimal medium composition for xylanase production by Aspergillus niger XY-1 in solid-state fermentation (SSF). Statistical methodology including the Plackett-Burman design (PBD) and the central composite design (CCD) was employed to investigate the individual crucial component of the medium that significantly affected the enzyme yield. Firstly, NaNO(3), yeast extract, urea, Na(2)CO(3), MgSO(4), peptone and (NH(4))(2)SO(4) were screened as the significant factors positively affecting the xylanase production by PBD. Secondly, by valuating the nitrogen sources effect, urea was proved to be the most effective and economic nitrogen source for xylanase production and used for further optimization. Finally, the CCD and response surface methodology (RSM) were applied to determine the optimal concentration of each significant variable, which included urea, Na(2)CO(3) and MgSO(4). Subsequently a second-order polynomial was determined by multiple regression analysis. The optimum values of the critical components for maximum xylanase production were obtained as follows: x(1) (urea)=0.163 (41.63 g/L), x(2) (Na(2)CO(3))=-1.68 (2.64 g/L), x(3) (MgSO(4))=1.338 (10.68 g/L) and the predicted xylanase value was 14374.6 U/g dry substrate. Using the optimized condition, xylanase production by Aspergillus niger XY-1 after 48 h fermentation reached 14637 U/g dry substrate with wheat bran in the shake flask. By using PBD and CCD, we obtained the optimal composition for xylanase production by Aspergillus niger XY-1 in SSF, and the results of no additional expensive medium and shortened fermentation time for higher xylanase production show the potential for industrial utilization.


Selective complexing of the "nuclear" 5S estradiol receptor by a serum component, 5S-CA.
A component present in several sera interacts selectively with the 5S "nuclear" form of estradiol receptor but not with the 4S "cytosol" form. This component is therefore referred to as "5S-complexing activity (5S-CA)." This selective interaction occurs with 5S receptor from mouse, calf, or rat. In addition, 5S-CA recognizes the nuclear form of the receptor from hypothalamic as well as uterine tissue Thus, 5S-CA indicates a general similarity in the chemical nature of 5S nuclear receptors prepared from several sources. Using 5S-CA as a chemical probe for the nuclear form of the estradiol receptor, I have shown the chemical as well as physical similarity of 5S receptors prepared in vivo (by injection of [3H]estradiol and subsequent isolation from nuclear/myofibrillar extracts) and in vitro (by labeling of cytoplasmic extracts and subsequent chromatography on columns of DNA-cellulose). These results indicate a distinctive chemical property of nuclear 5S forms of estradiol receptor. The data are interpreted with regard to models for 5S receptor formation. 5S-CA was found in sera from animals immunized against various antigens. The importance of testing for 5S-CA in antisera directed against steroid derivatives, steroid receptors, and other steroid-binding proteins is discussed.


Evaluation of a Clinical Policy Learning Activity.
Student groups compare evidence-based practice (EBP) to actual practice defined by hospital policies in their clinical rotation sites. This article describes a pilot study evaluating this clinical learning activity. Student and faculty surveys were developed and piloted. Purposive sampling with the surveys produced qualitative data and basic statistics to evaluate the learning activity. This study suggests that students' satisfaction with the clinical learning activity was generally positive. Three themes emerged, including Relevance to Clinical Practice, Course Outcomes Met, and Reinforcement of Evidence-Based Practice. Faculty surveys showed this learning activity was a useful tool for students to learn and utilize EBP. The learning activity is an effective learning and teaching strategy. Collaboration among nursing students, faculty, librarian, and nurses enhanced students' understanding of evidence related to policies in nursing practice and create a meaningful experience. Further work will focus on validation of the surveys. [J Nurs Educ. 2018;57(1):44-48.].


Advanced characterisation of encapsulated lipid powders regarding microstructure by time domain-nuclear magnetic resonance.
Encapsulation is an established technique to protect sensitive materials from environmental stress. In order to understand the physical protection mechanism against oxidation, knowledge about the powder microstructure is required. Time domain-nuclear magnetic resonance (TD-NMR) has the potential to determine the surface oil (SO) and droplet size distribution by relaxation and restricted self-diffusion, respectively. The amount of SO, the retention and encapsulation efficiency are determined based on a lipid balance. The oil load of the initial powder and after SO removal is measured by TD-NMR. The results correlate with gravimetric and photometric references. The oil droplet size obtained by TD-NMR correlates well with static light scattering. The diameter of droplets in emulsions and dried powder both measured by TD-NMR, correlates (r = 0.998), implying that oil droplets embedded in a solid matrix can be measured. Summarising, TD-NMR allows analysis of the microstructure of encapsulated lipid powders, in a rapid, simple and non-destructive way.


[The expression of Basigin mRNA in early ischemic myocardium and non-ischemic myocardium].
To investigate the expression of Basigin mRNA in early ischemic myocardium (EIM) and non-ischemic myocardium (NIM) in rat. Real-time polymerase chain reaction (PCR) technique was applied for detecting Basigin mRNA and beta-actin expression in EIM and NIM at 0 min, 15 min, 30 min, and 60 min. No significant differences of the Basigin mRNA expression in EIM and NIM between 0 min and sham operation (SO) or non-operation group (P > 0.05) were observed. Basigin mRNA expression in EIM significantly decreased in 15 min, 30 min, and 60 min group compared with that of 0 min group, respectively (P < 0.001). However, we failed to find any significant difference in NIM and NO from 0 min to 60 min. Basigin mRNA expression in EIM decreased significantly compared with that of in NIM (P < 0.05) after myocardial ischemia for 30 min. Basigin was involved in myocardium pathophysiology process after myocardial ischemia for 30 min, indicating that Basigin may be identified as a predictor of early myocardial ischemia in forensic medicine.


Biophysical support for functionally distinct cell types in the frontal eye field.
Numerous studies have described different functional cell types in the frontal eye field (FEF), but the reliability of the distinction between these types has been uncertain. Studies in other brain areas have described specific differences in the width of action potentials recorded from different cell types. To substantiate the functionally defined cell types encountered in FEF, we measured the width of spikes of visual, movement, and visuomovement types of FEF neurons in macaque monkeys. We show that visuomovement neurons had the thinnest spikes, consistent with a role in local processing. Movement neurons had the widest spikes, consistent with their role in sending eye movement commands to subcortical structures such as the superior colliculus. Visual neurons had wider spikes than visuomovement neurons, consistent with their role in receiving projections from occipital and parietal cortex. These results show how structure and function of FEF can be linked to guide inferences about neuronal architecture.


[First experience with elbasvir/grazoprevir fixed-dose combination in real-life practice in the Czech Republic].
Hepatitis C virus infection (HCV) is one of the leading causes of chronic liver disease worldwide. The new fixed-dose combination of the highly potent second wave first generation NS5A inhibitor elbasvir (50 mg) and the second generation protease inhibitor grazoprevir (100 mg) is contained in the drug Zepatier. This combination is indicated for the treatment of patients chronically infected with HCV genotypes 1 or 4. Between June and August 2017, the treatment was initiated in 22 patients with chronic viral hepatitis C, with 17 patients being treated in the Department of Infectious Diseases University Hospital Brno and five patients in the Center of Cardiovascular and Transplant Surgery in Brno. All patients were infected with HCV subtype 1b. In all cases, the duration of Zepatier monotherapy (without simultaneous ribavirin administration) was 12 weeks. At the moment, only preliminary results are available. All 22 patients achieved end-of-treatment virologic response. In nine patients, it was already possible to evaluate the virologic response at four weeks after the end of treatment, with sustained virological response (SVR12) was observed in all these patients. The most common complaints were fatigue (3 patients, 14 %) and headache (2.9 %). These problems were not serious and did not interfere with normal daily activities of treated persons.


Effectiveness and safety of vildagliptin and vildagliptin add-on to metformin in real-world settings in Egypt - results from the GUARD study.
The GUARD study evaluated the effectiveness, safety, and tolerability of vildagliptin treatment with or without metformin in patients with type 2 diabetes mellitus (T2DM) in real-life settings. Here we present the results of the GUARD study for the patient subset from Egypt. This was a 24 ± 6 weeks, prospective, non-interventional study that enrolled adult patients with T2DM receiving vildagliptin or vildagliptin + metformin combination therapy as per local prescribing information. The primary effectiveness endpoint was change in HbA1c levels from baseline to week 24 ± 6 endpoint. Safety was assessed by reporting of adverse events and serious adverse events (SAEs). Of 2786 patients enrolled from Egypt, 655 received vildagliptin and 2131 received vildagliptin + metformin. Overall, at baseline, mean (± standard deviation [SD]) age was 49.5 ± 9.49 years, BMI was 31.5 ± 4.85 kg/m2, HbA1c was 8.4 ± 0.86%, and duration of T2DM was 2.3 ± 3.78 years. At week 24, significant reductions in mean (±SD) HbA1c were observed in the vildagliptin (-1.47 ± 0.79%) and vildagliptin + metformin (-1.62 ± 0.82%) groups (both p < 0.0001) from baseline HbA1c of 8.1% and 8.4%, respectively. At week 24, 67.5% patients in the vildagliptin group and 60.5% in the vildagliptin + metformin group achieved HbA1c ≤7.0%. Treatment with vildagliptin (± metformin) was well tolerated, with a low incidence of hypoglycemia in both groups (vildagliptin, 0.5%; vildagliptin + metformin, 0.6%). No SAEs or deaths were reported in the vildagliptin group; however, 0.2% of patients experienced SAEs and one death (accidental death) was reported in the vildagliptin + metformin group. In a real-world setting, vildagliptin, with or without metformin, resulted in significant reductions in HbA1c and was well tolerated in patients with T2DM from Egypt. Limitations of the study include non-randomization and the open-label, observational nature of the study.


Comparison of HL-A typing with NIH trays and the NIH technique with typing by the fluorochromasia cytotoxicity assay.
A comparison of HL-A phenotypes determined with plates containing predispensed typing sera supplied by the NIH Serum Bank with phenotypes determined by the fluorochromasia cytotoxicity assay using local reagents showed that the NIH plates (as dispensed in 1972) had an insufficient number and variety of typing sera. Using NIH trays, it was difficult to detect HL-A9 and W19, both of which specificities are now known to have subtypes. The NIH trays also appeared to detect more HL-A antigens than were consistent with the current theory of two segregant series, each expressing a maximum of two antigens. The excess antigens could not be comparatively evaluated in view of the small number of sera defining each. With the NIH technique, it was impossible to interpret the reactions if the preparation had too many dead cells. A high proportion of dead cells was occasionally noted when lymphocytes had been previously frozen or obtained from lymph nodes. When the NIH and fluorochromasia techniques were compared using the same antisera and fresh lymphocytes, they proved equivalent in sensitivity.


Theoretical aspects of P-glycoprotein mediated drug efflux on the distribution volume of anaesthetic-related drugs in the brain.
P-glycoprotein in the membranes of endothelial cells actively transports some drugs out of the brain. The theoretical effect of P-glycoprotein mediated drug efflux on the cerebral distribution volumes of drugs was examined, with particular emphasis on anaesthetic-related drugs (often characterized by moderate to high permeability across the blood brain barrier due to their lipophilicity and intermediate molecular weight). An analytical equation for the cerebral distribution volume in the presence of the efflux was derived, and validated by modelling the same system using differential equations. The efflux was shown to lower both the membrane and intracellular drug concentrations in parallel, and to reduce the time required for brain:blood equilibration. The net effect of the efflux was governed by the ratio of the P-glycoprotein drug clearance from the membrane (Pcl) and the permeability of the membrane (PS). It was therefore a balance between the rate that a drug could be pumped out of the membrane by the efflux system, and the rate that the drug leaked back in due to the permeability of the membrane for the drug. The effect of the efflux was therefore more pronounced for drugs with membrane-limited cerebral kinetics (e.g. morphine), but was nevertheless significant for drugs with more flow-limited kinetics (e.g fentanyl). The cerebral distribution volume was also influenced by the free fraction in blood and the free fraction in the intracellular space in the conventional manner. There are no theoretical limitations to the P-glycoprotein system influencing the cerebral distribution volume of moderately lipophilic anaesthetic-related drugs.


Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation.
The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) mediates innate immune responses against invading pathogens, or against self-dsDNA, which causes autoimmune disorders. Upon nonspecific binding of cytosolic B-form DNA, cGAS synthesizes the second messenger 2'3'-cGAMP and triggers STING-dependent signaling to produce type I IFNs. The cGAS comprises less-conserved N-terminal residues and highly conserved nucleotidyltransferase/Mab21 domains. The function and structure of the well-conserved domains have been extensively studied, whereas the physiological function of the N-terminal domain of cGAS is largely uncharacterized. In this study we used a single-molecule technique combined with traditional biochemical and cellular assays to demonstrate that binding of nonspecific dsDNA by the N-terminal domain of cGAS promotes its activation. We have observed that the N terminus of human cGAS (hcGAS-N160) undergoes secondary structural change upon dsDNA binding in solution. Furthermore, we showed that the hcGAS-N160 helps full length hcGAS to expand the binding range on λDNA and facilitates its binding efficiency to dsDNA compared with hcGAS without the 160 N-terminal residues (hcGAS-d160). More importantly, hcGAS-N160 endows full length hcGAS relatively higher enzyme activity and stronger activation of STING/IRF3-mediated cytosolic DNA signaling. These findings strongly indicate that the N-terminal domain of cGAS plays an important role in enhancing its function.


Ethics of health promotion and health education.
Although in the last twenty years there has been an increasing interest in medical ethics, this has been centered around clinical problems and therapeutic medicine. However equally or more important are the ethical dilemmas arising in the field of health promotion and health education. These are described and commented upon.


The Campylobacter pylori story.
The Campylobacter pylori story began before the turn of the century, with early works describing 'spirochaetes' in the gastric mucosa of animals. Culture of the organism in 1982 enabled investigators to make sense of the many previous works concerning the microbiology, biochemistry, and histology of the gastric mucosa. Whereas some physicians remain skeptical of C. pylori's pathogenic role, those who have studied the new organism believe it is a major gastrointestinal pathogen and see the possibility of curative therapy for what is now called 'acid peptic disease'.


Sterile leukocyturia affects urine neutrophil gelatinase-associated lipocalin concentration in type 2 diabetic patients.
Increased urine neutrophil gelatinase-associated lipocalin (uNGAL) concentrations are associated with the early phase of kidney damage. Urine NGAL may increase due to production by neutrophils present in urine, particularly in patients with urinary tract infections. The aim of the study was to assess the relationship between sterile leukocyturia and uNGAL concentrations in patients with type 2 diabetes (DMt2) at early stages of diabetic kidney disease. The study included 115 DMt2 patients aged 60.0 ±15.5 years, with albuminuria < 300 mg/g creatinine and estimated glomerular filtration rate ≥ 60 ml/min/1.73 m² prospectively recruited at the nephrology ambulatory clinic in 2014-2015. The exclusion criteria were urinary tract infections (excluded by urine culture) and other diseases influencing uNGAL, including inflammatory and other kidney diseases. Urine concentrations of NGAL, albumin and creatinine were measured in the first morning samples, and the urine albumin to creatinine ratio (UACR) and uNGAL to creatinine ratio (UNCR) were calculated. Leukocyturia was detected microscopically. Sterile leukocyturia was present in 15% (95% confidence interval: 9-23%) of patients. Patients with leukocyturia had higher uNGAL and UNCR than patients without leukocyturia. ln(UNCR) correlated with ln(UACR) in the whole group (R = 0.59; p < 0.001) and in patients without leukocyturia (R = 0.56; p < 0.001). In multiple regression, age, ln(UACR), ln(HbA1c) and leukocyturia were independent positive predictors of ln(UNCR). Among patients with leukocyturia, the associations of UNCR with UACR, age and HbA1c were non-significant. In patients with DMt2, the presence of sterile leukocyturia coexists with increased uNGAL and UNCR. Leukocyturia interferes with the relationship between UNCR and UACR or HbA1c.


Investigation of MIF gene promoter variations and their haplotypes in the Alzheimer disease in Turkish population.
In Alzheimer's disease, which is characterized by amyloid plaques and neurofibrillary tangles in the brain tissue, many components such as acute phase proteins, cytokines, and proteases contribute to the progression of the disease or are part of the pathological process. The macrophage migration inhibitory factor (MIF) gene encodes a cytokine, which is secreted by lymphocytes, and has a role in the pathogenesis of autoimmune/inflammatory diseases such as rheumatoid arthritis. The purpose of this study to investigate the association between Alzheimer disease and MIF gene promoter polymorphisms. The 205 patients with Alzheimer disease (AD) and 130 age-sex matched healthy individuals were investigated in terms of MIF -173 G/C and MIF -794 CATT polymorphisms. The genotyping of MIF -173 G/C was determined using the RT-PCR method. MIF-794 CATT polymorphism was analyzed using PCR and DNA Sequencing. In terms of binary genotypes and haplotypes, the 5/5-GC (p = 0.004), 6/7-GG (p = 0.02) and, 6/6-GG (p = 0.026) binary genotypes, and 5-C (p = 0.003), 7-G (p = 0.026) and 6-G (p = 0.025) haplotypes were differed significantly between the patients and the controls. This is the first study investigating the relationship between AD and MIF in terms of different genotypes, haplotypes and, alleles. The fact that the binary genotype and allele distributions are significantly different between the patient and control group, suggests that this MIF variants may play a role in the pathogenesis of AD.


Mutations at the activated protein C cleavage sites Arg336 and Arg562 of factor VIII in Thai patients with venous thrombosis.
Venous thrombosis is a multicausal disease, more than one genetic risk factor may cooperate to effect thrombotic risk. Factor V Leiden is found to be an important hereditary risk factor for venous thromboembolism. Analogous to factor V Leiden, a point mutation at amino acid positions Arg336 and Arg562 in factor VIII may predispose patients to thrombosis. Eighty-one Thai patients with venous thrombosis and 100 Thai healthy volunteers have been studied. Neither heterozygous nor homozygous mutations were detected both thrombosis patients or normal volunteers. However, further studies with larger samples of venous thrombosis patients are recommended.


Genome-wide scan for circulating vascular adhesion protein-1 levels: MACROD2 as a potential transcriptional regulator of adipogenesis.
Vascular adhesion protein-1 (VAP-1) is a membrane-bound amine oxidase highly expressed in mature adipocytes and released into the circulation. VAP-1 has been strongly implicated in several pathological processes, including diabetes, inflammation, hypertension, hepatic steatosis and renal diseases, and is an important disease marker and therapeutic target. Here, we aimed to identify the genetic loci for circulating VAP-1 levels. We carried out a genomic-wide linkage scan for the quantitative trait locus of circulating VAP-1 levels in 1,100 Han Chinese individuals from 398 families in the Stanford Asian Pacific Program for Hypertension and Insulin Resistance study. Regional association fine mapping was carried out using additional single-nucleotide polymorphisms. The estimated heritability of circulating VAP-1 levels is high (h2 = 69%). The most significant quantitative trait locus for circulating VAP-1 was located at 38 cM on chromosome 20, with a maximum empirical logarithm of odds score of 4.11 (P = 6.86 × 10-6 ) in females. Regional single-nucleotide polymorphism fine mapping within a 1-unit support region showed the strongest association signals in the MACRO domain containing 2 (MACROD2) gene in females (P = 5.38 × 10-6 ). Knockdown of MACROD2 significantly suppressed VAP-1 expression in human adipocytes, as well as the expression of key adipogenic genes. Furthermore, MACROD2 expression was found to be positively associated with VAP-1 in human visceral adipose tissue. MACROD2 is a potential genetic determinant of serum VAP-1 levels, probably through transcriptional regulation of adipogenesis.


Pioneering particle-based strategy for isolating viable bacteria from multipart soil samples compatible with Raman spectroscopy.
The study of edaphic bacteria is of great interest, particularly for evaluating soil remediation and recultivation methods. Therefore, a fast and simple strategy to isolate various bacteria from complex soil samples using poly(ethyleneimine) (PEI)-modified polyethylene particles is introduced. The research focuses on the binding behavior under different conditions, such as the composition, pH value, and ionic strength, of the binding buffer, and is supported by the characterization of the surface properties of particles and bacteria. The results demonstrate that electrostatic forces and hydrophobicity are responsible for the adhesion of target bacteria to the particles. Distinct advantages of the particle-based isolation strategy include simple handling, enrichment efficiency, and the preservation of viable bacteria. The presented isolation method allows a subsequent identification of the bacteria using Raman microspectroscopy in combination with chemometrical methods. This is demonstrated with a dataset of five different bacteria (Escherichia coli, Bacillus subtilis, Pseudomonas fluorescens, Streptomyces tendae, and Streptomyces acidiscabies) which were isolated from spiked soil samples. In total 92% of the Raman spectra could be identified correctly.


Hypoxia induces dysregulation of local renin-angiotensin system in mouse Lewis lung carcinoma cells.
The renin-angiotensin system (RAS) influences cancer biology and is frequently dysregulated in malignancy. However, regulation of tumor local RAS remains poorly understood. Hypoxia is a hallmark of solid tumors and affects nearly every major aspect of cancer biology. Previous studies have shown that hypoxia can regulate RAS expression in somatic tissues and cells. The aim of this study was to investigate the influence of hypoxia on local RAS expression in mouse Lewis lung carcinoma (LLC) cells. For hypoxia treatment, LLC cells were cultured in a hypoxia incubator or treated with hypoxia-mimetic cobalt chloride. Hypoxia up-regulated angiotensin II, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R), and down-regulated ACE2 and angiotensin II type 2 receptor in LLC cells. Captopril, an ACE inhibitor, and losartan, an AT1R blocker, decreased expression of ACE and AT1R, but increased expression of ACE2 and angiotensin II type 2 receptor in LLC cells under hypoxia. Captopril and losartan also suppressed vascular endothelial growth factor-A expression in LLC cells under hypoxia. These findings suggest that hypoxia induces dysregulation of local RAS in LLC cells. The pathophysiological importance of hypoxia-induced RAS dysregulation and potentially therapeutic effects of RAS inhibitors on hypoxic tumor cells should be further examined.


Familial Essential Thrombocythemia Associated with MPL W515L Mutation in Father and JAK2 V617F Mutation in Daughter.
Familial essential thrombocythemia features the acquisition of somatic mutations and an evolution similar to the sporadic form of the disease. Here we report two patients-father and daughter-with essential thrombocythemia who displayed a heterogeneous pattern of somatic mutations. The JAK2 V617F mutation was found in the daughter, while the father harbored the MPL W515L mutation. This case report may constitute further proof that in familial essential thrombocythemia there are other, still undefined, constitutional, inherited genetic factors predisposing to the acquisition of various somatic mutations (e.g., JAK2 V617F and MPL).


An Aminopyrimidone and Aminoimidazoles Alkaloids from the Rodrigues Calcareous Marine Sponge Ernsta naturalis.
A chemical study of the CH2Cl2-MeOH (1:1) extract from the sponge Ernsta naturalis collected in Rodrigues (Mauritius) based on a molecular networking dereplication strategy highlighted one novel aminopyrimidone alkaloid compound, ernstine A (1), seven new aminoimidazole alkaloid compounds, phorbatopsins D-E (2, 3), calcaridine C (4), naamines H-I (5, 7), naamidines J-K (6, 8), along with the known thymidine (9). Their structures were established by spectroscopic analysis (1D and 2D NMR spectra and HRESIMS data). To improve the investigation of this unstudied calcareous marine sponge, a metabolomic study by molecular networking was conducted. The isolated molecules are distributed in two clusters of interest. Naamine and naamidine derivatives are grouped together with ernstine in the first cluster of twenty-three molecules. Phorbatopsin derivatives and calcaridine C are grouped together in a cluster of twenty-one molecules. Interpretation of the MS/MS spectra of other compounds of these clusters with structural features close to the isolated ones allowed us to propose a structural hypothesis for 16 compounds, 5 known and 11 potentially new.


Cathepsin B aggravates coxsackievirus B3-induced myocarditis through activating the inflammasome and promoting pyroptosis.
Cathepsin B (CatB) is a cysteine proteolytic enzyme widely expressed in various cells and mainly located in the lysosomes. It contributes to the pathogenesis and development of many diseases. However, the role of CatB in viral myocarditis (VMC) has never been elucidated. Here we generated the VMC model by intraperitoneal injection of coxsackievirus B3 (CVB3) into mice. At day 7 and day 28, we found CatB was significantly activated in hearts from VMC mice. Compared with the wild-type mice receiving equal amount of CVB3, genetic ablation of CatB (Ctsb-/-) significantly improved survival, reduced inflammatory cell infiltration, decreased serum level of cardiac troponin I, and ameliorated cardiac dysfunction, without altering virus titers in hearts. Conversely, genetic deletion of cystatin C (Cstc-/-), which markedly enhanced CatB levels in hearts, distinctly increased the severity of VMC. Furthermore, compared with the control, we found the inflammasome was activated in the hearts of wild-type mice with VMC, which was attenuated in the hearts of Ctsb-/- mice but was further enhanced in Cstc-/- mice. Consistently, the inflammasome-initiated pyroptosis was reduced in Ctsb-/- mice hearts and further increased in Cstc-/- mice. These results suggest that CatB aggravates CVB3-induced VMC probably through activating the inflammasome and promoting pyroptosis. This finding might provide a novel strategy for VMC treatment.


Lithium-catalyzed hydroxide attack at the carbon atom of methyl phosphate.
The spontaneous hydrolysis of phosphate ester monoanions is relatively easy, but the reaction of water with simple phosphate ester dianion appears to be the slowest biomimetic reaction whose spontaneous rate has been measured in water, with an estimated half time of approximately 1012 years at room temperature in the absence of a catalyst. Here, we report an alternative mode of cleavage of methyl phosphate that involves hydroxide attack at the carbon atom of methyl phosphate and proceeds at a rate proportional to the square of the concentration of lithium hydroxide.


Utility of the NavX® Electroanatomic Mapping System for Permanent Pacemaker Implantation in a Pregnant Patient with Chagas Disease.
Chagas disease is a highly prevalent zoonosis in Mexico, Central, and South America. Early cardiac involvement is one of the most serious complications of this disease, and conduction disturbances may occur at an early age. We describe a young pregnant woman with Chagas disease and a high degree atrioventricular block, who required implantation of a permanent dual chamber pacemaker. Using an electroanatomic navigation EnSite NavX® system the pacemaker was successfully implanted with minimal fluoroscopic exposure. This case demonstrates the safety and feasibility of using an electroanatomic navigation system to guide permanent pacemaker implantation minimizing x-ray exposure in pregnant patients.


Effectiveness of phosphodiesterase-5 inhibitor therapy for portopulmonary hypertension.
Portopulmonary hypertension is associated with significant morbidity and mortality. Phosphodiesterase-5 inhibitor therapy is efficacious in other causes of WHO group I pulmonary arterial hypertension. To evaluate the efficacy and safety of phosphodiesterase-5 inhibitor therapy in patients with portopulmonary hypertension. A single-centre retrospective cohort study that included patients with a diagnosis of portopulmonary hypertension was performed. The primary outcome was change in pulmonary vascular resistance after six months of phosphodiesterase-5 inhibitor therapy. A secondary evaluation investigated the effect on other hemodynamic measurements, 6 min walk distance, functional class, safety outcomes and survival. Of 1385 patients screened, 25 patients with portopulmonary hypertension were identified, of whom 20 received a phosphodiesterase-5 inhibitor. After six months, there was a significant decrease in pulmonary vascular resistance (-236 dyn • s • cm(-5) [95% CI -343 dyn • s • cm(-5) to -130 dyn • s • cm(-5)]; P<0.001), mean pulmonary artery pressure (-8.9 mmHg [95% CI -13.7 mmHg to -4.2 mmHg]; P=0.001) and an increase in Fick cardiac output (0.9 L/min [95% CI 0.1 L/min to 1.6 L/min]; P=0.02). There was no change in 6 min walk distance. The proportion of subjects with a WHO functional class III or IV was significantly reduced at six months compared with baseline (18% versus 61%; P=0.002). Safety outcomes did not reveal any adverse events. Phosphodiesterase-5 inhibitor therapy improved hemodynamics and functional class at six months in a cohort of patients with portopulmonary hypertension.


Intramedullary spinal cord tumours presenting as scoliosis.
Intramedullary spinal cord tumours may present as scoliosis without neurological signs. Those treating spinal deformities should be alert to this possible aetiology. The clinical features of 12 such cases are discussed with reference to early diagnosis and treatment. Patients with a painful scoliosis should be investigated with myelography as well as bone scintigraphy. Many intrinsic spinal cord tumours are now amenable to surgical removal. The prognosis for neurological recovery is poor once a severe deficit becomes established. The importance of early diagnosis and joint orthopaedic and neurosurgical management is emphasised.


Thyrotropin effects on ultraviolet radiation-dependent apoptosis in FRTL-5 cells.
Apoptosis plays an important role within the endocrine system, particularly in the thyroid gland, although little is known about its regulation in normal thyroids. Because thyrotropin (TSH) regulates many thyroid-specific functions and cell proliferation, we investigated whether TSH can influence such mechanisms. To induce apoptosis we used UV-C radiation. The FRTL-5 rat thyroid cell strain, a cloned strain of differentiated and untransformed cells that reproduces many of the characteristics of the normal thyroid was chosen for this study. The FRTL-5 cells are a particularly suitable model because they actively proliferate when cultured in the presence of TSH (6H medium), while in TSH-free medium (5H medium) cells remain in a physiologic quiescent state for a long period of time. FRTL-5 cells in both culture conditions were irradiated with UV-C radiation (254 nm wavelength). At 48 hours after radiation, 6H cultured cells showed the characteristic signs of apoptosis. However, 5H cultured cells did not present macroscopic signs of damage, DNA fragmentation, or detectable apoptosis. Furthermore, the expression of 23 apoptosis-related genes was compared. Results indicate that Bcl2 and caspase-2 expression is enhanced, while bax, GADD45 and mdm-2 expression is reduced in irradiated cells. These data confirm that TSH plays a major role in regulating UV-induced apoptosis in FRTL-5 cells.


Does differential prophylactic aspirin use contribute to racial and geographic disparities in stroke and coronary heart disease (CHD)?
Aspirin use may reduce the risk of stroke and coronary heart disease. Differential use for vascular prophylaxis may contribute to racial and geographic disparities in stroke and coronary heart disease morbidity or mortality. To assess the prevalence and predictors of aspirin use for primary prophylaxis of stroke in the general population free of clinically diagnosed stroke or coronary heart disease. Cross-sectional analysis of 16,908 participants (age 45 or greater), from a population-based national cohort study (REasons for Geographic And Racial Differences in Stroke) enrolled from February 2003-August 2006 with oversampling from the southeastern Stroke Belt and African Americans. Individuals with a prior stroke or coronary heart disease, or regular use of aspirin for pain relief were excluded from analyses. Aspirin use and reasons for use were assessed using a computer-assisted telephone interview. Prophylactic aspirin use was substantially higher among whites (34.7%) than African Americans (27.2%; p<0.0001). There was a higher prevalence of aspirin use for prophylaxis in the Stroke Belt (32.1%) than in the rest of the nation (30.8%; p=0.07). After adjustment for measures of socio-economic status, the odds ratio of aspirin use in the rest of the nation compared to Stroke Belt was 0.90 (95% CI 0.84-0.97). There was a higher likelihood of prophylactic aspirin use among participants who were white, male, older, past cigarette smokers, or of higher socio-economic status (higher income or education). In this study, aspirin use to prevent stroke and coronary heart disease was higher among whites than African Americans, raising the possibility that differential aspirin use could contribute to the racial disparities in vascular disease mortality. Counter to our hypothesis, aspirin use was more common in the Stroke Belt than the rest of the country, so differential aspirin use in the Stroke Belt is unlikely to contribute to geographic disparities in stroke.


Canadian medicine: dominance or proletarianization?
Changes in the Canadian health care system since the early 1960s, especially the introduction of national health insurance and increased government control over the cost and utilization of services, have been resisted by the medical profession. The history of the conflicts between the Canadian government and the medical profession over control of the health care system provides evidence that medical dominance has declined. In spite of its loss of power over the organization of health care and medical work, however, the profession is still too powerful to be described as proletarianized. Freidson's theoretical conception of professional dominance provides the best explanation of the position of Canadian physicians, but his argument that power is preserved by having physicians control other physicians fails to take into account the profession's lack of internal cohesion.


Susceptibility of various animals to the vesiculovirus Piry.
To determine the pathogenic potential of the vesiculovirus Piry for domestic animals, two ponies, two steers, three sheep, three goats and three pigs were inoculated intradermally in the tongue or, in the case of the pigs, in the snout, heel and coronary band. Inoculated animals were housed in one room and allowed to mingle freely with an equal number of uninoculated contact animals of each species. Clinical signs of infection, consisting of elevated temperature and ulcers at the inoculation sites, were only observed in the ponies, but all inoculated animals developed specific antibody following inoculation. In addition, one of the contact sheep had neutralizing antibody to Piry at 7 and 29 days post inoculation suggesting a contact infection. Virus was not demonstrated in tissues, other than tongue, of any animal. The failure of Piry virus to produce lesions in steers, sheep, goats and pigs and only limited ulcerations in ponies suggests that this virus is not similar pathogenically to New Jersey and Indiana strains of vesiculoviruses which produce classical vesicular stomatitis. Lethal infections were produced by inoculation into suckling mice and hamsters, adult hamsters and embryonating chicken eggs. Further, lethal infections followed contact of adult female hamsters with their inoculated litters.


Cyclic Distannene or Bis(stannylene) with a Ferrocenyl Backbone: Synthesis, Structure, and Coordination Chemistry.
1,1'-Dilithioferrocene was reacted with 2 equiv of isopropyl (Ar*) or methyl (Ar') substituted terphenyl tin(II) chloride. Reaction product 1, carrying the bulkier terphenyl substituent Ar*, displays a bis(stannylene) structure in the solid state without formation of a tin-tin bond. Temperature-dependent solution 119Sn NMR spectroscopy, however, revealed a dynamic interplay between bis(stannylene) (100 °C) and cyclic distannene (-80 °C). In contrast to 1, the less bulky Ar' substituent results in a cyclic distannene 2. On the basis of temperature-dependent 119Sn NMR spectroscopy the Sn-Sn bond of compound 2 was preserved up to 100 °C. Both compounds were further characterized by solid-state 119Sn NMR spectroscopy as well as 119Sn and 57Fe Mössbauer spectroscopy. 1 reacted as a chelating ligand with nickel and palladium complexes [Ni(cod)2] and [Pd(nbe)3] (nbe = norbornene). In the resulting coordination compounds the nonstabilized stannylene acts as a donor as well as an acceptor ligand and shows a dynamic switch from donor to acceptor behavior in the monopalladium complex.


Multi-Ethnic Attitudes Toward Physician-Assisted Death in California and Hawaii.
As aid-in-dying laws are gaining more public acceptance and support, it is important to understand diverse perceptions toward physician-assisted death (PAD). We compare attitudes of residents from California and Hawaii to identify variables that may predict attitudes toward PAD. A cross-sectional online survey of 1095 participants (a 75.8% survey completion rate) from California and 819 from Hawaii (a 78.4% survey completion rate). Data were collected between July through October 2015. Majority of study participants in California (72.5%) and Hawaii (76.5%) were supportive of PAD. Only 36.8% of participants in Hawaii and 34.8% of participants in California reported completing advance directives. To better understand which subgroups were most in favor of PAD, data were analyzed using both recursive partitioning and stepwise logistic regression. Older participants were more supportive of PAD in both states. Also, all ethnic groups were equally supportive of PAD. Completion of advance directives was not a significant predictor of attitudes toward PAD. Persons who reported that faith/religion/spirituality was less important to them were more likely to support PAD in both states. Thus, the major influences on the attitudes to PAD were religious/spiritual views and age, not ethnicity and gender. Even in the subgroups least supportive of PAD, the majority supported PAD. This study shows that in the ethnically diverse states of California and Hawaii, faith/religion/spirituality and age are major influencers of attitudes toward PAD and not ethnicity and gender. Even in the subgroups least supportive of PAD, the majority supports PAD.


The influence of retinol concentration in liquid crystal formula on epidermal growth factor, interleukin-6 and transglutaminase-1 mRNA expression in the epidermis.
Topical retinol application effectively reduces the effects of photoaging and improves skin condition, e.g. influences the process of keratinization of the epidermis, which improves stratum corneum structure and reduces transepidermal water loss. However, cosmetics use lower concentrations of retinol, which has been associated with emerging hypersensitivity reactions as well as redness and irritation of the skin. The question arises whether the vehicle used in the cosmetic may be important in stimulating the inflammatory reaction in the skin and if the concentration of retinol used could significantly affects the growth of epidermal cells. The aim of this study was to evaluate the effects of different concentrations of liquid crystal retinol (0.15%, 0.3% and 0.5%) on the clinical and histological characteristics of a reconstructed epidermis skin model. It also compares the effectiveness of 0.3% retinol formula in liquid crystal to that in lipid. The study used reconstructed human epidermis tissue containing normal human keratinocytes. Four original formulas containing retinol were tested: 0.15%, 0.3% and 0.5% with a liquid crystal base, and 0.3% with a lipid base. Interleukin 6 (IL-6), transglutaminase-1 (TGM1), and epidermal growth factor (EGF) mRNA expression was measured expression of the skin-equivalent tissue for 10 days of exposure. Histopathological analysis and mRNA quantification were performed. Gene expression was analyzed by total mRNA extraction. All liquid crystal formulas induced higher EGF mRNA expression than lipid base formula. IL-6 expression did not differ significantly from the DPBS reference values. Interestingly, TGM1 expression was found to increase together with increasing retinol concentration (0.15%, 0.3%, 0.5%). Histological examination revealed changes in epidermal structure, mainly hyperkeratinization of the stratum corneum. Our results support the hypothesis liquid crystal formula might be regarded as more beneficial since it inducess less pro-inflammatory action manifested by lowered expression IL-6. In addition, EGF expression was found to correlate significantly with the retinol concentration of the liquid crystal formula: 0.5% > 0.3% > 0.15% (P < 0.05). Lower concentrations may increase TGM1 expression, thus enhancing the formation of a protective layer of cornified envelope.


Dietary wolfberry ameliorates retinal structure abnormalities in db/db mice at the early stage of diabetes.
Hyperglycemia-linked oxidative stress and/or consequent endoplasmic reticulum (ER) stress are the causative factors of pathogenesis of diabetic retinopathy. Dietary bioactive components which mitigate oxidative stress may serve as potential chemopreventive agents to prevent or slow down the disease progression. Wolfberry is a traditional Asian fruit consumed for years to prevent aging eye diseases in Asian countries. Here we report that dietary wolfberry ameliorated mouse retinal abnormality at the early stage of type 2 diabetes in db/db mice. Male mice at six weeks of age were fed the control diet with or without 1% (kcal) wolfberry for eight weeks. Dietary wolfberry restored the thickness of the whole retina, in particular the inner nuclear layer and photoreceptor layer, and the integrity of the retinal pigment epithelia (RPE), and the ganglion cell number in db/db mice. Western blotting of whole retinal cell lysates revealed that addition of wolfberry lowered expression of ER stress biomarkers binding immunoglobulin protein (BiP), protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and caspase-12, and restored AMP-activated protein kinase (AMPK), thioredoxin, Mn superoxide dismutase (Mn SOD) and forkhead O transcription factor 3 α (FOXO3α) activities. To determine if our observations were due to the high contents of zeaxanthin and lutein in wolfberry, additional studies using these carotenoids were conducted. Using the human adult diploid RPE cell line ARPE-19, we demonstrated that both zeaxanthin and lutein could mimic the wolfberry preventive effect on activation of AMPK, thioredoxin, Mn SOD, FOXO3α activities, normalize cellular reactive oxygen species and attenuate ER stress in ARPE-19 cells exposed to a high glucose challenge. The zeaxanthin preventive effect was abolished by small interfering RNA knockdown of AMPKα. These results suggested that AMPK activation appeared to play a key role in upregulated expression of thioredoxin and Mn SOD, and mitigation of cellular oxidative stress and/or ER stress by wolfberry and zeaxanthin and/or lutein. Taken together, dietary wolfberry on retinal protection in diabetic mice is, at least partially, due to zeaxanthin and/or lutein.


Porphyrin Metalation at the MgO Nanocube/Toluene Interface.
Molecular insights into porphyrin adsorption on nanostructured metal oxide surfaces and associated ion exchange reactions are key to the development of functional hybrids for energy conversion, sensing, and light emission devices. Here we investigated the adsorption of tetraphenyl-porphyrin (2HTPP) from toluene solution on two types of MgO powder. We compare MgO nanocubes with an average size d < 10 nm and MgO cubes with 10 nm ≤ d ≤ 1000 nm. Using molecular spectroscopy techniques such as UV/vis transmission and diffuse reflectance (DR), photoluminescence (PL), and diffuse reflectance infrared Fourier-transform (DRIFT) spectroscopy in combination with structural characterization techniques (powder X-ray diffraction and transmission electron microscopy, TEM), we identified a new room temperature metalation reaction that converts 2HTPP into magnesium tetraphenyl-porphyrin (MgTPP). Mg(2+) uptake from the MgO nanocube surfaces and the concomitant protonation of the oxide surface level off at a concentration that corresponds to roughly one monolayer equivalent adsorbed on the MgO nanocubes. Larger MgO cubes, in contrast, show suppressed exchange, and only traces of MgTPP can be detected by photoluminescence.


Two gene fragments that direct podocyte-specific expression in transgenic mice.
Transgenic manipulation of the glomerular visceral epithelial cell offers a powerful approach for studying the biology of this morphologically complex cell type. It has been previously demonstrated that an 8.3-kb and a 5.4-kb fragment of the murine Nphs1 (nephrin) promoter-enhancer drives lacZ expression in podocytes, brain, and pancreas of transgenic mice, recapitulating the expression pattern of the endogenous nephrin gene. In this present study, two truly podocyte-specific promoters were identified that drive transgene expression in podocytes without expression in extrarenal tissues in adult or embryonic mice. A 1.25-kb fragment driving a lacZ reporter gene (p1.25N-nlacF) was derived from murine Nphs1 promoter similar to a human NPHS1 promoter fragment previously reported. Transgenic mice were generated and beta-galactosidase (beta-gal) expression was analyzed. Four of twelve founder mice were found to express beta-gal in podocytes (33% penetrance). Expression in brain and pancreas was absent in all animals, suggesting that nephrin expression in these organs might be driven by distinct cis-regulatory elements that can be removed to obtain podocyte-specific expression. A 2.5-kb fragment derived from the human NPHS2 (podocin) gene was designed in a similar fashion to drive lacZ expression in transgenic mice (p2.5P-nlacF). Twelve of twlve NPHS2 mouse founder lines expressed beta-gal exclusively in podocytes (100% penetrance). Beta-gal activity was not observed extrinsic to the kidney in p1.25N-nlacF or p2.5P-nlacF mouse embryos at gestational time points between 8.5 d post coitus and birth. In conclusion, the 2.5-kb NPHS2 promoter fragment may be useful for podocyte-specific transgenic expression when extrarenal expression of a transgene is problematic.


Potential Biomarkers of Peripheral and Central Fatigue in High-Intensity Trained Athletes at High-Temperature: A Pilot Study with Momordica charantia (Bitter Melon).
Among potent dietary supplements, Momordica charantia, commonly called bitter melon, has various biological effects, such as antioxidant and anti-inflammatory effects, and improves energy metabolism and fatigue recovery. However, it is unknown whether Momordica charantia extract (MCE) induces antifatigue effects during exercise training in high-temperature environments. This study aimed at investigating the efficacy of MCE by examining 10 male tennis players consuming 100 mL MCE/dose (6 times a day over 4 weeks) during the summer training season. Peripheral (ammonia and uric acid) and central (serotonin, dopamine, and prolactin) fatigue parameters were measured before and after MCE consumption; before, during, and after exercise; and the next morning. After consuming MCE supplements, ammonia levels were higher during and after exercise and recovered the next morning, whereas uric acid levels did not change at any time point. Serotonin levels were lower during exercise. Dopamine levels were higher, especially during exercise. Prolactin levels were lower at all time points, especially during and after exercise. Although high-intensity training in a hot environment causes accumulation of fatigue-related metabolites, our results indicate that 4 weeks of MCE intake positively influenced fatigue parameters, suggesting that MCE can efficiently combat fatigue.


[A case of left main coronary artery stenosis: additional insertion of saphenous vein graft to discontinue cardiopulmonary bypass].
A 62-year-old man with the lesions of the left main coronary artery and all the three vessels underwent a complete revascularization, in which the left internal mammary artery (IMA) was anastomosed to the large LAD. Although the operation proceeded uneventfully, the patient could not be weaned from the cardiopulmonary bypass (CPB). Another saphenous vein graft insertion into the LAD just distal to the IMA made it possible to discontinue the CPB. Postoperative angiogram revealed the patency of all grafts. But the IMA graft showed flow competition and string sign. We assume that failure to wean the patient from the CPB might be caused by hypoperfusion of the IMA graft, and in such a case, insertion of a saphenous vein graft is effective.


Expression and regulation of neuropilins and VEGF receptors by TNF-alpha in human endothelial cells.
Recently, neuropilins (NRPs) were identified as new VEGF receptors (VEGFRs) and VEGFR-3 was revealed to be implicated in angiogenesis besides in lymphangiogenesis. However, quantitative expression and regulation of NRPs and VEGFRs remain unclear. The objective of this study was to compare the expression of NRPs and VEGFRs and investigate their regulation by tumor necrosis factor (TNF-alpha) in human endothelial cells (ECs) as well as their roles in VEGF(165)-induced EC proliferation. Human umbilical vein ECs (HUVECs) were treated with TNF-alpha (2 ng/ml) or PBS for 24 h. The mRNA and protein levels of NRP-1, NRP-2, VEGFR-1, VEGFR-2, and VEGFR-3 were semiquantitatively determined by real-time PCR and Western blot, respectively. Real-time PCR data were presented as the difference of reaction cycle thresholds (Ct) between beta-actin and each of the genes of interest (2(-DeltaCt)). EC proliferation in response to VEGF(165) (10 ng/ml) with or without anti-VEGFR-2 neutralization antibody pretreatment was analyzed by [(3)H]thymidine incorporation. In PBS-treated HUVECs, mRNA levels of NRPs and VEGFRs were NRP-1 (0.013), NRP-2 (0.007), VEGFR-2 (0.006), VEGFR-1 (0.0024), and VEGFR-3 (0.0009). After TNF-alpha treatment, mRNA levels of VEGFR-2, VEGFR-3, and NRP-1 were significantly reduced by 72, 65, and 53%, respectively (P < 0.05). The protein expression of all NRPs and VEGFRs were also detected by Western blot. TNF-alpha significantly reduced protein levels of VEGFR-2, VEGFR-3, and NRP-1 by 59, 35, and 22%, respectively. However, both mRNA and protein levels of VEGFR-1 and NRP-2 were not affected by TNF-alpha. Furthermore, TNF-alpha treatment significantly reduced EC proliferation in response to VEGF(165) by 67%. After blocking VEGFR-2 with neutralization antibody, TNF-alpha treatment elicited a 30% reduction of EC proliferation in response to VEGF(165). These data demonstrate that HUVECs express higher mRNA levels of NRP-1 and NRP-2 than those of VEGFRs, and TNF-alpha treatment significantly decreases the expression of VEGFR-2, VEGFR-3, and NRP-1, which may be responsible for TNF-alpha-induced reduction of EC proliferation in response to VEGF(165).


Atomic Scale Imaging of Reversible Ring Cyclization in Graphene Nanoconstrictions.
We present an atomic level study of reversible cyclization processes in suspended nanoconstricted regions of graphene that form linear carbon chains (LCCs). Before the nanoconstricted region reaches a single linear carbon chain (SLCC), we observe that a double linear carbon chain (DLCC) structure often reverts back to a ribbon of sp2 hybridized oligoacene rings, in a process akin to the Bergman rearrangement. When the length of the DLCC system only consists of ∼5 atoms in each LCC, full recyclization occurs for all atoms present, but for longer DLCCs we find that only single sections of the chain are modified in their bonding hybridization and no full ring closure occurs along the entire DLCCs. This process is observed in real time using aberration-corrected transmission electron microscopy and simulated using density functional theory and tight binding molecular dynamics calculations. These results show that DLCCs are highly sensitive to the adsorption of local gas molecules or surface diffusion impurities and undergo structural modifications.