Gold-Iron oxide yolk-shell nanoparticles (YSNPs) as magnetic probe for fluorescence-based detection of 3 base mismatch DNA.
Seed-mediated Gold-Iron oxide yolk-shell nanoparticles (YSNPs) were synthesized and functionalized with cy5 attached- thiolated single strand DNA probe for the detection of mutated DNA. The optimum concentration of thiolated DNA determined from a bathochromic shift of surface plasmon resonance (SPR) peak, was 0.177μM. The effect of pH (2-10), temperature (4, 37, 60 and 100 °C), and ionic strengths (1 M to 4 M) on the stability of ssDNA probe tethered YSNPs, studied with the assistance of flocculation parameter. The detection of mutation in DNA was possible using such ssDNA probe functionalized and stabilized nanoparticles. The hybridization of the oligonucleotide probe with the complementary, non-complementary and mutated DNA strands are determined via their respective intensities of the fluorescence of cy5, an efficient fluorescent marker. The intensities help in the comprehension of the specificity of the system. The report predicts controlled efficiency of hybridization with the aid of Hamaker constant, which is determined as 1.15 × 10-20 J for DNA functionalized YSNPs. The minimum concentration of target DNA detected using this methodology was 1.2 × 10-11 mol/L.


Respiration of mammalian cells at low concentrations of oxygen: I. Effect of hypoxic-cell radiosensitizing drugs.
Drugs which sensitize hypoxic mammalian cells to radiation damage in vitro can also affect the cellular respiration rate. This phenomenon was studied in detail to determine whether the changes in oxygen consumption occur at low oxygen concentrations and under optimal nutritional conditions. We have found that cells in tissue culture can undergo adaptive changes in respiration (electron flow) which make them insensitive to the effects of radiosensitizing drugs and even respiration uncouplers such as dinitrophenol, and the inhibitors rotenone and cyanide. At low cell densities, where nutrient depletion in the medium would be negligible, the drugs have reduced effects, particularly at low oxygen concentrations (below 40 mmHg oxygen partial pressure). Parallel cytotoxicity and growht inhibition studies indicate that most drugs are unlikely to have substantial effect on respiration at non-cytotoxic levels.


The effect of nitrous oxide on S-adenosylmethionine levels in mouse brain.
Mice were exposed to nitrous oxide (50%) for up to 24 h and S-adenosylmethionine (SAMe) levels measured in corpus striatum and cerebellum, areas with high and low catecholamine turnover rates, respectively. After 4 h, levels were 21 and 8% and after 6 h, 33 and 14% lower than controls in striatum and cerebellum, respectively. Thus, the effect was more pronounced in corpus striatum, the area with the presumed higher rate of catecholamine O-methylation. With continued exposure to nitrous oxide SAMe concentrations in the two areas returned to nearly normal at 24 h. The observation that levels did not continue to decline, and even returned towards control levels, while animals were still in the presence of the gas suggests that a mechanism other than that of methionine synthase inhibition may have been responsible for the initial effect. Alternatively, some other source of SAMe may have become available to compensate for the inhibition of the enzyme.


Chemical Footprinting Reveals Conformational Changes Following Activation of Factor XI.
Coagulation factor XI is activated by thrombin or factor XIIa resulting in a conformational change that converts the catalytic domain into its active form and exposing exosites for factor IX on the apple domains. Although crystal structures of the zymogen factor XI and the catalytic domain of the protease are available, the structure of the apple domains and hence the interactions with the catalytic domain in factor XIa are unknown. We now used chemical footprinting to identify lysine residue containing regions that undergo a conformational change following activation of factor XI. To this end, we employed tandem mass tag in conjunction with mass spectrometry. Fifty-two unique peptides were identified, covering 37 of the 41 lysine residues present in factor XI. Two identified lysine residues that showed altered flexibility upon activation were mutated to study their contribution in factor XI stability or enzymatic activity. Lys357, part of the connecting loop between A4 and the catalytic domain, was more reactive in factor XIa but mutation of this lysine residue did not impact on factor XIa activity. Lys516 and its possible interactor Glu380 are located in the catalytic domain and are covered by the activation loop of factor XIa. Mutating Glu380 enhanced Arg369 cleavage and thrombin generation in plasma. In conclusion, we have identified novel regions that undergo a conformational change following activation. This information improves knowledge about factor XI and will contribute to development of novel inhibitors or activators for this coagulation protein.


Print-Light-Synthesis for Single-Step Metal Nanoparticle Synthesis and Patterned Electrode Production.
The fabrication of thin-film electrodes, which contain metal nanoparticles and nanostructures for applications in electrochemical sensing as well as energy conversion and storage, is often based on multi-step procedures that include two main passages: (i) the synthesis and purification of nanomaterials and (ii) the fabrication of thin films by coating electrode supports with these nanomaterials. The patterning and miniaturization of thin film electrodes generally require masks or advanced patterning instrumentation. In recent years, various approaches have been presented to integrate the spatially resolved deposition of metal precursor solutions and the rapid conversion of the precursors into metal nanoparticles. To achieve the latter, high intensity light irradiation has, in particular, become suitable as it enables the photochemical, photocatalytical, and photothermal conversion of the precursors during or slightly after the precursor deposition. The conversion of the metal precursors directly on the target substrates can make the use of capping and stabilizing agents obsolete. This review focuses on hybrid platforms that comprise digital metal precursor ink printing and high intensity light irradiation for inducing metal precursor conversions into patterned metal and alloy nanoparticles. The combination of the two methods has recently been named Print-Light-Synthesis by a group of collaborators and is characterized by its sustainability in terms of low material consumption, low material waste, and reduced synthesis steps. It provides high control of precursor loading and light irradiation, both affecting and improving the fabrication of thin film electrodes.


[DISSEMINATED CARCINOMATOSIS OF THE BONE MARROW WITH UROTHELIAL CARCINOMA].
Disseminated carcinomatosis of the bone marrow with urothelial carcinoma in a 75-year-old man: A case study. A 75-year-old-man had first medical examination due to gross hematuria. The imaging study and cystoscopy revealed left ureteral and bladder tumor. The patient was referred for a laparoscopic assisted left nephroureterectomy and transurethral resection of a bladder tumor (TUR-Bt). Pathological findings included urothelial carcinoma, high grade, both a pT3 ureteral tumor and a pTa bladder tumor. The patient received 2 courses of gemcitabine and cisplatin and 1 course of methotrexate, epirubicin and nedaplatin as adjuvant chemotherapy. TUR-Bt was performed twice due to recurrence in the bladder and similar pathological findings. The patient received intravesical instillation of pirarubicin (THP 30 mg in 30 mL of saline) to prevent recurrence in the bladder, but discontinued in the 3rd time because of gross hematuria. The patient was then admitted to our hospital due to gross hematuria, general fatigue, and abnormal findings in the blood analysis. On admission, pancytopenia was detected and the serum ALP level had increased to 30,266 IU/L. A biopsy and bone marrow aspiration were performed because a super bone scan image was obtained using a bone scintigram. Diffuse bone marrow metastasis of the urothelial carcinoma was observed in the pathological evaluations. Therefore, our diagnosis was urothelial carcinoma with disseminated carcinomatosis of the bone marrow. Although treatment with zoledronic acid and blood transfusion were performed, the patient died 20 days after the admission. To the best of our knowledge, this is the first case of disseminated carcinomatosis of the bone marrow with urothelial carcinoma.


Detection of minimal residual disease in cerebro-spinal fluid of a patient with acute myelogenous leukemia with t(16;21)(p11;q22) translocation by reverse transcriptase-polymerase chain reaction.
We describe a patient with acute myelogenous leukemia (AML) with t(16;21)(p11;q22) translocation, whose minimal residual disease (MRD) both in cerebrospinal fluid (CSF) and bone marrow (BM) was monitored by reverse transcriptase-polymerase chain reaction (RT-PCR). A TLS/ERG-FUS fusion transcript, which is known to be expressed by t(16;21)(p11;q22) translocation, was detectable by RT-PCR both in BM and CSF cells in the first complete remission, suggesting the existence of MRD. The disease relapsed 6 months after its onset and allogeneic peripheral blood stem cell transplantation (PBSCT) was undergone. A TLS/ERG-FUS fusion transcript became rapidly below the detection level after PBSCT. These findings suggest the usefulness of RT-PCR for the detection of MRD in CSF, which contains a limited number of cells, as well as BM.


Determination of oxygen adsorption-desorption rates and diffusion rate coefficients in perovskites at different oxygen partial pressures by a microkinetic approach.
A novel, powerful method based on a microkinetic approach is described for the estimation of the oxygen transport parameters of mixed electronic conducting materials (MIECs). This method is validated on the perovskite La0.6Sr0.4Co0.2Fe0.8O3-δ and has been applied on Ba0.5Sr0.5Co0.8Fe0.2O3-δ. This approach is original and relevant in that the surface kinetic rate constants are measured using a sample in powder form. In contrast to methods previously used, such as isotope exchange depth profiling (IEDP) and electrical conductivity relaxation (ECR), which determine the global exchange kinetic parameter, our microkinetic modelling approach allows the estimation of the forward and reverse kinetic rates accounting for the oxygen vacancy concentration. Also, the self-diffusion rate coefficient has been estimated at different oxygen partial pressures. This microkinetic approach, which combines SSITKA (steady-state isotopic transient kinetic analysis) and thermogravimetric measurements at controlled oxygen partial pressure, has the potential to significantly accelerate the characterization of oxygen transport in perovskites and related materials in the future. In this study, the kinetic parameters were measured in a temperature window between 873 K and 1173 K, and at two oxygen pressure conditions (21 kPa and 1 kPa) that are appropriate for simulating the semi-permeability of oxygen in a membrane in a process of oxygen separation from air.


Lung cancer and angiogenesis imaging using synchrotron radiation.
Early detection of lung cancer is the key to a cure, but a difficult task using conventional x-ray imaging. In the present study, synchrotron radiation in-line phase-contrast imaging was used to study lung cancer. Lewis lung cancer and 4T1 breast tumor metastasis in the lung were imaged, and the differences were clearly shown in comparison to normal lung tissue. The effect of the object-detector distance and the energy level on the phase-contrast difference was investigated and found to be in good agreement with the theory of in-line phase-contrast imaging. Moreover, 3D image reconstruction of lung tumor angiogenesis was obtained for the first time using a contrast agent, demonstrating the feasibility of micro-angiography with synchrotron radiation for imaging tumor angiogenesis deep inside the body.


Expression of a 46 kDa protein in human pancreatic tumors and its possible relationship with the bile salt-dependent lipase.
Bile salt-dependent lipase (BSDL), an enzyme normally found in human pancreatic secretions is a 100 kDa glycoprotein. A BSDL-specific 477 bp cDNA probe was prepared by performing polymerase chain reaction experiments. This cDNA was used to probe mRNAs extracted from human pancreatic tissue and tumoral cell lines. Two mRNAs were detected in normal human pancreas at 2.2 and 1.3 to 1.5 kb. In human pancreatic tumoral cells, mRNAs encoding for the BSDL were detected using in situ hybridization, and proteins with an M(r) of 46,000 to 48,000 were translated into an in vitro system using mRNAs extracted from these cells. Using an immunoprecipitation procedure, we observed here that the specific BSDL polyclonal antibodies recognized three proteins of 100 +/- 5 (p100), 46 +/- 2 (p46) and 22.7 +/- 1.2 (p23) kDa, respectively in the soluble extracts of normal adult human pancreas. The p100 protein was probably the glycosylated product resulting from the translation of the 2.2 kb transcript. The p46 protein, which electrophoresed as a doublet was the main component immunoprecipitated from extract of a differentiated human pancreatic adenocarcinoma as well as from the extracts of two pancreatic cell lines, BxPC-3 and SOJ-6. In addition, the p46 immunoform of the BSDL was detected in cell-free medium from SOJ-6 cell line and its expression was found to be correlated with the secretion of an esterolytic activity on 4-nitrophenyl caproate, whereas the BxPC-3 cell line neither secreted the p46 nor showed any esterolytic activity on this substrate. The p46 may be either a short variant of BSDL resulting from the translation of the 1.3 to 1.5 kb transcript or a protein structurally related to the enzyme. The p46 doublet immunoform was detected in the human pancreatic secretion.


Physiological effects of shift work on hospital nurses.
The purpose of this study was to assess the physiological effects of shift work on the urinary excretion rates of norepinephrine, 6-sulfatoxymelatonin and estriol in hospital nurses. Twenty-four hour urine specimens were examined on a daytime/nighttime basis for each work shift of pregnant and non-pregnant subjects. The urinary norepinephrine and 6-sulfatoxymelatonin were measured by enzyme-linked immunosorbent assay and estriol by radio-immunoassay. Urinary norepinephrine level during the night work was higher than the night levels of the days off and the day shift. Urinary 6-sulfatoxymelatonin level during the night work was lower than the night levels of the days off and the day shift. Urinary estriol level of pregnant subjects showed no differences among work shift and also between daytime and nighttime. Urinary excretion rates of norepinephrine and 6-sulfatoxymelatonin were affected by shift work both for non-pregnant and pregnant subjects. It was unlikely that urinary estriol levels in the pregnant subjects were significantly affected by shift work.


A fully biocompatible single-mode distributed feedback laser.
A fully biocompatible laser would be attractive in many aspects of biomedical research. Here we report a single-mode biocompatible distributed feedback laser consisting of silk, riboflavin and silver in the form of a freestanding film. The distributed feedback structure has a large surface area and flexibility. The fabricated laser exhibited single-mode lasing at a wavelength of 495 nm.


Water Load Test in Children with Chronic Abdominal Pain or Obesity Compared with Nonobese Controls.
Satiety is the perception of satisfied fullness and represents a summation of neural and hormonal influences. Satiety can be assessed by drink tests, including water load. The objective of our study was to confirm the difference in water load volume between nonobese control children and children with functional dyspepsia (FD), children with irritable bowel syndrome (IBS), and obese children. A total of 158 children ages 6 to 13 years participated in the study. There were 43 children with FD, 25 with IBS, 44 obese children, and 46 nonobese age-matched control children. Subjects drank as much water as possible in 3 minutes or until their stomachs felt full. Children in the FD and IBS groups drank less water than did the nonobese controls; the obese children drank more water than did the nonobese controls. The water load test demonstrated high specificity but poor sensitivity in predicting children with FD. A water load test offers a simple, noninvasive research tool to measure satiety. Children with chronic abdominal pain drank less than nonobese control children; however, the water load test did not discriminate between FD and IBS. Obese children drank more water than the other groups, suggesting the possibility of an underlying abnormality in the perception of satiety.


[Distribution and infectious characteristics of re-positive cases infected with SARS-CoV-2].
Domestic and foreign literatures related to the persistence of SARS-CoV-2 and the re-positive cases infected with SARS-CoV-2 were reviewed, and the characteristics and infectivity of the re-positive cases were analyzed to provide scientific evidence for the improvement of case management and the development of measures to stop the spread of SARS-CoV-2. Existing studies have shown that re-positive rate of SARS-CoV-2 ranged from 2.4% to 19.8%, the median of interval between re-positive detection and discharge was 4-15 days. Following the second course of the disease, the anti-SARS-CoV-2 IgM, IgG and IgA positive rates of the cases were 11.11%-86.08%, 52.00%-100.00% and 61.54%-100.00% respectively, the total antibody and neutralizing antibody positive rates were 98.72% and 88.46%. The viral load of the re-positive cases was lower than that in the initial infection. At least 3 380 re-positive cases have been reported globally. SARS-CoV-2 strains were isolated from the samples of 3 re-positive cases (1 immunodeficiency case and 2 cases with abnormal pulmonary imaging). There were close contacts that were infected by an asymptomatic case taking immunosuppressive agents. In conclusion, the infectivity of re-positive cases infected with SARS-CoV-2 is generally very low. Rare re-positive cases infected with SARS-CoV-2 might cause further transmission. The management approach for the re-positive cases can be based on the assessment of the individual transmission risk according to the pathogen detection results.


Low concentrations of nitric oxide exert a hormetic effect on Mycobacterium tuberculosis in vitro.
Susceptibilities of 12 clinical Mycobacterium tuberculosis isolates to acidified sodium nitrite (ASN) were compared. The results demonstrate that 8 of the 12 isolates exhibited enhanced survival levels in 1.5 mM ASN compared to levels in medium alone, suggesting that low concentrations of reactive nitrogen intermediates have a hormetic effect on M. tuberculosis in vitro.


Homotopic Action: A Pathway to Convergent Diagrammatic Theories.
The major obstacle preventing Feynman diagrammatic expansions from accurately solving many-fermion systems in strongly correlated regimes is the series slow convergence or divergence problem. Several techniques have been proposed to address this issue: series resummation by conformal mapping, changing the nature of the starting point of the expansion by shifted action tools, and applying the homotopy analysis method to the Dyson-Schwinger equation. They emerge as dissimilar mathematical procedures aimed at different aspects of the problem. The proposed homotopic action offers a universal and systematic framework for unifying the existing-and generating new-methods and ideas to formulate a physical system in terms of a convergent diagrammatic series. It eliminates the need for resummation, allows one to introduce effective interactions, enables a controlled ultraviolet regularization of continuous-space theories, and reduces the intrinsic polynomial complexity of the diagrammatic Monte Carlo method. We illustrate this approach by an application to the Hubbard model.


Extracting textural features from tactile sensors.
This paper describes an experiment to quantify texture using an artificial finger equipped with a microphone to detect frictional sound. Using a microphone to record tribological data is a biologically inspired approach that emulates the Pacinian corpuscle. Artificial surfaces were created to constrain the subsequent analysis to specific textures. Recordings of the artificial surfaces were made to create a library of frictional sounds for data analysis. These recordings were mapped to the frequency domain using fast Fourier transforms for direct comparison, manipulation and quantifiable analysis. Numerical features such as modal frequency and average value were calculated to analyze the data and compared with attributes generated from principal component analysis (PCA). It was found that numerical features work well for highly constrained data but cannot classify multiple textural elements. PCA groups textures according to a natural similarity. Classification of the recordings using k nearest neighbors shows a high accuracy for PCA data. Clustering of the PCA data shows that similar discs are grouped together with few classification errors. In contrast, clustering of numerical features produces erroneous classification by splitting discs between clusters. The temperature of the finger is shown to have a direct relation to some of the features and subsequent data in PCA.


A novel three-component reaction toward dihydrooxazolopyridines.
Isocyano dihydropyridones accessible via a recently reported multicomponent reaction react with aldehydes and amines to afford dihydrooxazolopyridines in high yield. The scope and limitations of this novel multicomponent reaction were investigated. The efficient combination of two highly variable multicomponent reactions allows the construction of a very broad range of dihydrooxazolopyridines, an unexplored class of bicyclic compounds. The implications of the observed reactivity profile for the mechanism of this multicomponent reaction are discussed.


Density Functional Theory Study of the Reaction between d0 Tungsten Alkylidyne Complexes and H2O: Addition versus Hydrolysis.
The reactions of early-transition-metal complexes with H2O have been investigated. An understanding of these elementary steps promotes the design of precursors for the preparation of metal oxide materials or supported heterogeneous catalysts. Density functional theory (DFT) calculations have been conducted to investigate two elementary steps of the reactions between tungsten alkylidyne complexes and H2O, i.e., the addition of H2O to the W≡C bond and ligand hydrolysis. Four tungsten alkylidyne complexes, W(≡CSiMe3)(CH2SiMe3)3 (A-1), W(≡CSiMe3)(CH2tBu)3 (B-1), W(≡CtBu)(CH2tBu)3 (C-1), and W(≡CtBu)(OtBu)3 (D-1), have been compared. The DFT studies provide an energy profile of the two competing pathways. An additional H2O molecule can serve as a proton shuttle, accelerating the H2O addition reaction. The effect of atoms at the α and β positions has also been examined. Because the lone-pair electrons of an O atom at the α position can interact with the orbital of the proton, the barrier of the ligand-hydrolysis reaction for D-1 is dramatically reduced. Both the electronic and steric effects of the silyl group at the β position lower the barriers of both the H2O addition and ligand-hydrolysis reactions. These new mechanistic findings may lead to the further development of metal complex precursors.


Transfer RNA genes in mycobacteria: organization and molecular cloning.
DNAs from nine mycobacterial species were cleaved with different restriction endonucleases and hybridized with cDNA probes synthesized to total transfer RNAs (tRNAs) from Mycobacterium smegmatis and M. tuberculosis. The hybridization data indicate that tRNA genes are conserved but their gross genomic organization has diverged in six of the nine species examined. Species of the MTB complex appeared to have identical tRNA gene organization. Hybridization with cDNAs synthesized to 23S plus 16S rRNAs from Escherichia coli indicate that the tRNA genes map near the rRNA genes. Recombinant plasmids, pSB1, pSB2, pSB4 and pSB8 encoding tRNA(s) and rRNA(s) were isolated from a gene bank of M. tuberculosis H37Rv. Using pSB2 as probe, a SalI RFLP was observed that distinguishes the virulent and avirulent strains of M. tuberculosis H37Rv and H37Ra, respectively.


Thin-section CT in obstructive pulmonary disease: discriminatory value.
To use thin-section computed tomography (CT) to distinguish between causes of obstructive pulmonary disease, to determine which distinctions give rise to diagnostic imprecision, and to identify the most useful CT features. Thin-section CT scans of 105 patients with obstructive pulmonary disease (asthma, n = 35; centrilobular emphysema, n = 30; panlobular emphysema, n = 21; and obliterative bronchiolitis, n = 19) and 33 healthy subjects were assessed independently by two observers. The most likely diagnosis and a confidence rating were assigned. Individual thin-section CT features were recorded. Accuracy, sensitivity, specificity, negative predictive value, and positive predictive value for first-choice diagnoses were calculated. The prevalence of CT features between pairs of conditions was compared with the chi(2) or Fisher exact test as appropriate. A correct first-choice diagnosis was made in 199 of 276 (72%) observations. A correct first-choice diagnosis was made in 35 of 38 (92%) observations in patients with obliterative bronchiolitis, in 53 of 60 (88%) observations in patients with centrilobular emphysema, in 53 of 66 (80%) observations in healthy subjects, in 37 of 70 (53%) observations in patients with asthma, and in 20 of 42 (48%) observations in patients with panlobular emphysema. The major sources of diagnostic inaccuracy were differentiation between panlobular and centrilobular emphysema, asthma and normality, and asthma and obliterative bronchiolitis. There were significant increases in prevalence of (a) bronchial wall thickening and vascular attenuation in patients with asthma when compared with healthy subjects and (b) vascular attenuation and decreased attenuation in patients with obliterative bronchiolitis when compared with patients with asthma (P <.001). CT helps to distinguish diseases that cause airflow obstruction. Thin-section CT is particularly accurate in the identification of obliterative bronchiolitis.


Identifying binary protein-protein interactions from affinity purification mass spectrometry data.
The identification of protein-protein interactions contributes greatly to the understanding of functional organization within cells. With the development of affinity purification-mass spectrometry (AP-MS) techniques, several computational scoring methods have been proposed to detect protein interactions from AP-MS data. However, most of the current methods focus on the detection of co-complex interactions and do not discriminate between direct physical interactions and indirect interactions. Consequently, less is known about the precise physical wiring diagram within cells. In this paper, we develop a Binary Interaction Network Model (BINM) to computationally identify direct physical interactions from co-complex interactions which can be inferred from purification data using previous scoring methods. This model provides a mathematical framework for capturing topological relationships between direct physical interactions and observed co-complex interactions. It reassigns a confidence score to each observed interaction to indicate its propensity to be a direct physical interaction. Then observed interactions with high confidence scores are predicted as direct physical interactions. We run our model on two yeast co-complex interaction networks which are constructed by two different scoring methods on a same combined AP-MS data. The direct physical interactions identified by various methods are comprehensively benchmarked against different reference sets that provide both direct and indirect evidence for physical contacts. Experiment results show that our model has a competitive performance over the state-of-the-art methods. According to the results obtained in this study, BINM is a powerful scoring method that can solely use network topology to predict direct physical interactions from AP-MS data. This study provides us an alternative approach to explore the information inherent in AP-MS data. The software can be downloaded from https://github.com/Zhangxf-ccnu/BINM.


[The so-called partial synchronization in the treatment of malignant lymphomas. A clinical study].
In a randomized study the effectiveness of a modified MOPP scheme (CVPP scheme) and a so-called partial synchronisation treatment (vincristine or vinblastine respectively and cyclophosphamide) was compared in 72 patients predominantly pretreated with Hodgkin lymphomas and non-Hodgkin lymphomas. From 49 patients affected with lymphogranulomatosis of stage IIIB and IV, 24 were treated according to CVPP scheme; in 10 of them a complete remission was achieved and in 4 of them a partial remission. 25 patients were treated in the control group with synchronization therapy. In 13 of them a complete remission and in 12 of them a partial remission was achieved. With CVPP therapy the mean remission time amounted to 14.4 months and with synchronization therapy 9.2 months. There was no significant statistical difference. From 23 patients with advanced non-Hodgkin lymphomas of a high malignancy 11 received a therapy with CVPP scheme; 2 of them came into a complete remission and 3 of them into a partial one. 12 patients received a synchronization therapy; 7 of them came into a partial remission. With CVPP therapy the mean remission time amounted to 14.4 months, with partial synchronization therapy--10.8 months. Even in non-Hodgkin lymphomas there was no significant difference between the forms of therapy used. Even a comparison of the two survival times of both forms of treatment does not reveal any significance. Thus, both procedures of treatment seem to be comparable in their therapeutic efficaciousness, even if the number of complete remissions during the treatment with CVPP scheme was greater in our investigations. The assumed lower toxicity of synchronization therapy could not be confirmed by our study. In addition to the controversial synchronization effect, the good efficaciousness of treatment according to the so-called synchronization therapy may be due to sensibilizing phenomena and recruitment phenomena.


Participation in the national cervical screening programme among women from New South Wales, Australia, by place of birth and time since immigration: A data linkage analysis using the 45 and up study.
Equitable elimination of cervical cancer in Australia within the next decade will require high National Cervical Screening Program (NCSP) participation by all subgroups of women. The aim of this study was to examine the participation of immigrants compared to Australian-born women. Participation in the NCSP (≥1cytology test) over a 3-year (2010-2012) and 5-year (2008-2012) period, by place of birth and time since immigration was examined using individually linked data of 67,350 New South Wales (NSW) women aged ≥45 enrolled in the 45 and Up Study. Three-year cervical screening participation was 77.0% overall. Compared to Australian-born women (77.8%), 3-year participation was lower for women born in New Zealand (adjusted odds ratio 0.77, 95% confidence interval 0.69-0.87), Oceania (0.67, 0.51-0.89), Middle East/North Africa (0.76, 0.60-0.97), South-East Asia (0.72, 0.60-0.87), Chinese Asia (0.82, 0.69-0.97), Japan/South Korea (0.68, 0.50-0.94), and Southern/Central Asia (0.54, 0.43-0.67), but higher for women from Malta (2.85, 1.77-4.58) and South America (1.33, 1.01-1.75). Non-English-speaking-at-home women were less likely to be screened than English-speaking-at-home women (0.85, 0.78-0.93). Participation increased with years lived in Australia but remained lower in immigrant groups compared to Australian-born women, even after ≥20 years living in Australia. Similar results were observed for 5-year participation. Women born in New Zealand, Oceania, and parts of Asia and the Middle East had lower NCSP participation, which persisted for ≥20 years post-immigration. The NCSP transition to primary HPV screening, and the introduction of the universal self-collection option in 2022, will offer new opportunities for increasing screening participation for these groups.


Tracking independence and merging of prosodic and phonemic processing across infancy.
Recent evidence suggests division of labor in phonological analysis underlying speech recognition. Adults and children appear to decompose the speech stream into phoneme-relevant information and into syllable stress. Here we investigate whether both speech processing streams develop from a common path in infancy, or whether there are two separate streams from early on. We presented stressed and unstressed syllables (spoken primes) followed by initially stressed early learned disyllabic German words (spoken targets). Stress overlap and phoneme overlap between the primes and the initial syllable of the targets varied orthogonally. We tested infants 3, 6 and 9 months after birth. Event-related potentials (ERPs) revealed stress priming without phoneme priming in the 3-month-olds; phoneme priming without stress priming in the 6-month-olds; and phoneme priming, stress priming as well as an interaction of both in 9-month-olds. In general the present findings reveal that infants start with separate processing streams related to syllable stress and to phoneme-relevant information; and that they need to learn to merge both aspects of speech processing. In particular the present results suggest (i) that phoneme-free prosodic processing dominates in early infancy; (ii) that prosody-free phoneme processing dominates in middle infancy; and (iii) that both types of processing are operating in parallel and can be merged in late infancy.


Polaromonas jejuensis sp. nov., isolated from soil in Korea.
A Gram-negative, rod-shaped, non-motile bacterial strain, designated JS12-13(T), was isolated from soil from Halla Mountain on Jeju Island, Korea. Analysis of the 16S rRNA gene sequence of strain JS12-13(T) revealed that it was a member of the genus Polaromonas, sharing 96.9-98.4 % sequence similarity with type strains of the genus Polaromonas and being most closely related to Polaromonas aquatica CIP 108776(T). The major fatty acids of strain JS12-13(T) were summed feature 3 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH; 38.3 %), C(16 : 0) (28.4 %), C(17 : 0) cyclo (15.9 %) and C(18 : 1)omega7c (9.1 %). The major quinone found was ubiquinone-8. The G+C content of the genomic DNA of strain JS12-13(T) was 63.7 mol%. On the basis of phenotypic and genotypic characteristics, strain JS12-13(T) represents a novel species of the genus Polaromonas, for which the name Polaromonas jejuensis sp. nov. is proposed. The type strain is JS12-13(T) (=KACC 12508(T) =DSM 19351(T)).


Periodontal awareness and knowledge, and pattern of dental attendance among adults in Jordan.
To provide baseline data on periodontal awareness and health knowledge, and to assess patterns of dental attendance behaviours among 20 to 60 year-old Jordanian adults. A questionnaire incorporating items related to personal and socio-demographic data, periodontal awareness and health knowledge, and self-reported dental attendance behaviours. One-thousand questionnaires were distributed among adults attending dental clinics. 743 questionnaires were completed and statistically analysed. About one-quarter of adults reported 'gum bleeding' on brushing, but more subjects (40.4%) believed that they had periodontal disease. Also, 47% of the participants thought that they had a 'rough tooth surface', 16% had 'gum irritation' and 25% had 'bad breath'. There were no statistically significant differences between genders with regard to responses on periodontal awareness (P >0.05). The majority of adults incorrectly defined the meaning of dental plaque and did not know its role in the aetiology of gingival disease. Conversely, the majority of participants (60.8%) were aware that gingival bleeding upon brushing indicated the presence of periodontal disease that can be prevented by brushing and flossing (63.4%), mainly before going to bed (73.9%). The overwhelming majority of subjects (81.4%) were irregular attenders. 'Treatment not necessary' and 'cost' were found to be the common barriers for regular dental attendance. The most common treatment received by the subjects at their last visit was restorative therapy. Knowledge and awareness concerning periodontal disease is still poor in Jordan, therefore, more dental health education is needed to improve oral health.


Intrinsic thermal expansivity and hydrational properties of amyloid peptide Abeta42 in liquid water.
Volumetric and conformational properties of the amyloid beta(1-42) peptide (Abeta(42)) are studied in relation to the properties of hydration water in a wide temperature range by computer simulations. The apparent volume of Abeta(42), which is the change in the total volume of the solution due to the presence of Abeta(42), shows a quite different temperature dependence below and above T approximately 320 K. The apparent thermal expansion coefficient alpha(app)(Abeta(42)) is about 1.5x10(-3) K(-1) at T<or=320 K and about 0.6x10(-3) K(-1) at T>320 K. By evaluation of the thermal expansivity of hydration water, the intrinsic expansivity of the biomolecule in liquid water was determined for the first time. The intrinsic thermal expansion coefficient of Abeta(42) is found to be negative: alpha(int)(Abeta(42)) approximately -0.8x10(-3) K(-1). The negative thermal expansion coefficient of Abeta(42) can be attributed to its rubberlike (entropic) elasticity and/or to a decreasing number of intrapeptide hydrogen bonds. Upon heating, Abeta(42) transforms from an extended chain with a significant content of alpha-helices to a compact coil with noticeable content of beta-structures. A hydrogen-bonded spanning network of hydration water envelops Abeta(42) homogeneously at low temperatures but breaks into an ensemble of small water clusters upon heating via a percolation transition, whose midpoint is close to the temperature, where the apparent volume of Abeta(42) changes its temperature behavior. The mutual relation between the volumetric properties of Abeta(42), its conformational properties, and the properties of the hydration water is discussed.


An unexpected cause of pulmonary hypertension in a young woman: a case report.
Pulmonary hypertension (PH) is defined as a progressive disease that leads to right heart failure and death if untreated. This case report presents a young woman with reversible precapillary PH in the setting of a gastric cancer. A 37-year-old woman presented with exertional dyspnoea and syncope. The transthoracic echocardiographic findings were consistent with a cor pulmonale. Right heart catheterization (RHC) proved a precapillary PH. Specific PH therapy with macitentan and tadalafil was initiated. Shortly thereafter, a gastric carcinoma was diagnosed, and oncologic treatment with neoadjuvant chemotherapy and subsequent gastrectomy was promptly initiated. Retrospectively, we considered a pulmonary tumour thrombotic microangiopathy the most probable cause of PH. Follow-up after successful oncologic treatment and cumulative 10 months of specific PH medication showed an excellent clinical response with complete remission of PH confirmed by RHC at rest. Tumour-related PH is very rare and might be largely underdiagnosed as the clinical course often results in a rapid deterioration and fatal outcome before diagnostics are completed. Post mortem studies have documented tumoural emboli in pulmonary microcirculation in ∼26% of patients with a solid tumour, markedly associated with adenocarcinoma. Prompt initiation of cancer treatment on tumoural PH is essential. To our knowledge, this report documents the first full recovery of tumoural PH at rest after successful cancer treatment and temporary specific PH medication. We therefore conclude that a multidisciplinary approach with an initially combined oncologic and PH therapy may be most beneficial with the potential of complete remission of PH.


Structure of nanocrystalline calcium silicate hydrates: insights from X-ray diffraction, synchrotron X-ray absorption and nuclear magnetic resonance.
The structure of nanocrystalline calcium silicate hydrates (C-S-H) having Ca/Si ratios ranging between 0.57 ± 0.05 and 1.47 ± 0.04 was studied using an electron probe micro-analyser, powder X-ray diffraction, 29Si magic angle spinning NMR, and Fourier-transform infrared and synchrotron X-ray absorption spectroscopies. All samples can be described as nanocrystalline and defective tobermorite. At low Ca/Si ratio, the Si chains are defect free and the Si Q3 and Q2 environments account, respectively, for up to 40.2 ± 1.5% and 55.6 ± 3.0% of the total Si, with part of the Q3 Si being attributable to remnants of the synthesis reactant. As the Ca/Si ratio increases up to 0.87 ± 0.02, the Si Q3 environment decreases down to 0 and is preferentially replaced by the Q2 environment, which reaches 87.9 ± 2.0%. At higher ratios, Q2 decreases down to 32.0 ± 7.6% for Ca/Si = 1.38 ± 0.03 and is replaced by the Q1 environment, which peaks at 68.1 ± 3.8%. The combination of X-ray diffraction and NMR allowed capturing the depolymerization of Si chains as well as a two-step variation in the layer-to-layer distance. This latter first increases from ∼11.3 Å (for samples having a Ca/Si ratio <∼0.6) up to 12.25 Å at Ca/Si = 0.87 ± 0.02, probably as a result of a weaker layer-to-layer connectivity, and then decreases down to 11 Å when the Ca/Si ratio reaches 1.38 ± 0.03. The decrease in layer-to-layer distance results from the incorporation of interlayer Ca that may form a Ca(OH)2-like structure, nanocrystalline and intermixed with C-S-H layers, at high Ca/Si ratios.


Linkage Between Databases in Joint Arthroplasty and Orthopaedics: The Way Forward?
Each large observational database contains specific data elements. The number of data elements are chosen carefully to cover the essential needs of the database as well as to avoid excessive burden of collection. Frequently, an important study question cannot be answered because one database does not contain some essential data elements. This deficiency may be present because the proposed study is cross-disciplinary, because the study requires more granular information on a specific topic than is practical to collect in a broad-based registry, or because the relevant questions, and hence essential data elements, have changed over time. An obvious way to overcome some such challenges, when one database contains some of the information and another contains the further needed data, is to link different databases. While the prospect of linking databases is appealing, the practicalities of doing so often are daunting. Challenges may be practical (information-technology barriers to crosstalk between the registries), legal, and financial. In the first section of this paper, Dr. Nathanael Heckmann discusses linking large orthopaedic databases, focusing on linking databases with detailed, short-term data to those with longer-term longitudinal data. In the second part of this paper, Nathan Glusenkamp discusses efforts to link the American Joint Replacement Registry (AJRR) to other data sources, an ambition not yet fully realized but one that will bear fruit in the near future.


A piezoelectric-sound-resonance cavity for hydrogen gas detection.
A new concept for hydrogen gas (H2) detection has been developed. This concept is based on a piezoelectric-sound-resonance cavity (PSRC). Detection uses sound resonance and the acoustic property differences of gases as a sensing mechanism in which there is a significant difference in the sound velocity and acoustic impedance between H2 and air. The PSRC sensor consists of two thin piezoelectric discs, separated by a small cavity. One disc excites a weak acoustic standing wave in the cavity, and the second senses the wave by monitoring the acoustic impedance characteristics of the cavity. Changes in H2 concentration result in a shift of the sound resonance state. Investigations of a PSRC prototype have demonstrated a sensitivity limit of <10 ppm, a fast response time approximately 1 second, and a signal (phase and voltage) in proportion to the change in H2 concentration (n) over the range of 10(-5) < n < 0.2. These performance characteristics are far superior to those of other methods.


Extracellular calmodulin-induced stomatal closure is mediated by heterotrimeric G protein and H2O2.
Extracellular calmodulin (ExtCaM) exerts multiple functions in animals and plants, but the mode of ExtCaM action is not well understood. In this paper, we provide evidence that ExtCaM stimulates a cascade of intracellular signaling events to regulate stomatal movement. Analysis of the changes of cytosolic free Ca2+ ([Ca2+]cyt) and H2O2 in Vicia faba guard cells combined with epidermal strip bioassay suggests that ExtCaM induces an increase in both H2O2 levels and [Ca2+]cyt, leading to a reduction in stomatal aperture. Pharmacological studies implicate heterotrimeric G protein in transmitting the ExtCaM signal, acting upstream of [Ca2+]cyt elevation, and generating H2O2 in guard cell responses. To further test the role of heterotrimeric G protein in ExtCaM signaling in stomatal closure, we checked guard cell responses in the Arabidopsis (Arabidopsis thaliana) Galpha-subunit-null gpa1 mutants and cGalpha overexpression lines. We found that gpa1 mutants were insensitive to ExtCaM stimulation of stomatal closure, whereas cGalpha overexpression enhanced the guard cell response to ExtCaM. Furthermore, gpa1 mutants are impaired in ExtCaM induction of H2O2 generation in guard cells. Taken together, our results strongly suggest that ExtCaM activates an intracellular signaling pathway involving activation of a heterotrimeric G protein, H2O2 generation, and changes in [Ca2+]cyt in the regulation of stomatal movements.


Hydrophobic affinity chromatography of nucleic acids and proteins. II. Activity of trityl Sepharose immobilized enzymes.
A variety of nucleic acid synthetic and degradative enzymes and proteases are shown to bind to trityl sepharose columns and, for the most part, retain moderate amounts of activity for periods of days to weeks. Non-covalent hydrophobic interactions are believed to be largely responsible for the observed binding and maintenance of activity. In addition the hydrophobic binding mechanism of poly A to trityl sepharose columns under a variety of conditions is compared with that to nitrocellulose columns and contrasted with that of dT cellulose columns.


Drug-resistant tuberculosis in Zhejiang Province, China: an updated analysis of time trends, 1999-2013.
Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) hinder the progress of TB control. To track the trend of drug-resistant tuberculosis (DR-TB) prevalence in Zhejiang Province from 1999 to 2013, and identify risk factors of resistance to second-line drugs among MDR-TB patients. Four DR-TB surveys had been done in Zhejiang Province in 1999, 2004, 2008 and 2013 through questionnaires, in which demographic and epidemiological items were included. After questionnaires, drug susceptibility testing (DST) targeted at four first-line drugs was done for all TB patients and DST targeted at six second-line drugs (only in 2008 and 2013) for MDR-TB patients. The drug resistance trend over time was analyzed using the Cochran-Armitage test. The factors associated with resistance to second-line drugs among MDR-TB patients were examined by a multivariate logistic regression model. Of 936 patients enrolled, 27 (3.21%) and 20 (21.28%) MDR-TB cases were registered as new and previously treated cases, respectively. MDR-TB showed a decreasing trend (Z = -3.31, p < 0.01) while resistance to any first-line drugs showed an increasing trend (Z = 5.22, p < 0.001), from 1999 to 2013. The highest resistance rate was shown to ofloxacin among MDR-TB patients both in 2008 (28.8%) and in 2013 (27.7%), while resistance to para-aminosalicylate decreased significantly (Z = -2.06, p = 0.04) between 2008 and 2013. MDR-TB patients aged 45-65 years (OR = 5.00, p = 0.02) were more likely to be resistant to any second-line drugs. DR-TB including MDR-TB remains a major public health problem in Zhejiang Province. Further efforts on MDR-TB control should be conducted to hinder drug resistance, including critical clinical use of anti-TB antibiotics and preventing transmission.


Left Anterior Mini-Incision for Pulmonary Valve Replacement Following Tetralogy of Fallot Repair.
Pulmonary insufficiency is a known complication following Tetralogy of Fallot repair. With over 90% of patients now surviving to adulthood, surgeons are once again faced with the question of when, and more importantly, how to reintervene. We developed a novel approach to pulmonary valve replacement in this population through a 5-cm left anterior mini-incision. The incision is optimized for exposing and operating on the right ventricular outflow tract and the main pulmonary artery in patients with a history of median sternotomy. Early outcomes are reassuring, and we believe our approach is a safe and reliable alternative to median sternotomy within this patient population, with the ability to quickly convert intraoperatively when needed.


Discovery and biological evaluation of a new family of potent modulators of multidrug resistance: reversal of multidrug resistance of mouse lymphoma cells by new natural jatrophane diterpenoids isolated from Euphorbia species.
The effects of 15 jatrophane diterpene polyesters (1-3 and 5-16) isolated from lipophilic extracts of Euphorbia serrulata, E. esula, E. salicifolia, and E. peplus (Euphorbiaceae) on the reversion of multidrug resistance of mouse lymphoma cells were examined. The structures of five new compounds (1-5) were elucidated by spectroscopic methods, including HRFABMS, ESIMS, (1)H-(1)H homonuclear and (1)H-(13)C heteronuclear correlations, long-range correlation spectra, and NOESY experiments. The stereochemistry and absolute configuration of one compound (3) were determined by X-ray crystallography. The structure-activity relationship is discussed.


Pindolol in hypertension: twice-daily versus thrice-daily dosage.
Afternood lying and standing blood pressure, pulse rate and plasma pindolol levels were measured twice, a month apart, in 16 cases in which hypertension was well controlled either by pindolol alone or by pindolol plus a diuretic. During the month preceding each observation, the daily dose of pindolol was given in either two or three divided doses. Plasma pindolol levels could be measured in only seven cases. In these, 4 p.m. plasma pindolol levels were significantly lower on the twice-daily dosage regimen. Mean afternoon lying and standing blood pressure and lying pulse rate values were slightly but not significantly higher on the twice-daily regimen. Mean standing pulse rates were significantly higher on the twice-daily regimen. It appears that, for the control of hypertension, pindolol can be given in a twice daily regimen in most cases.


Pre-mRNA splicing in cancer: the relevance in oncogenesis, treatment and drug resistance.
Aberrant pre-mRNA splicing in cancer is emerging as an important determinant of oncogenesis, response to treatment and anticancer drug resistance. At the same time, the spliceosome has become a target for a novel class of pre-clinical chemotherapeutics with a potential future application in cancer treatment. Taken together, these findings offer novel opportunities for the enhancement of the efficacy of cancer therapy. This review presents a comprehensive overview of the molecular mechanisms involved in splicing and current developments regarding splicing aberrations in relation to several aspects of cancer formation and therapy. Identified mutations in the various components of the spliceosome and their implications for cancer prognosis are delineated. Moreover, the contribution of abnormal splicing patterns as well as deregulated splicing factors to chemoresistance is discussed, along with novel splicing-based therapeutic approaches. Significant progress has been made in deciphering the role of splicing factors in cancer including carcinogenesis and drug resistance. Splicing-based prognostic tools as well as therapeutic options hold great potential towards improvements in cancer therapy. However, gaining more in-depth molecular insight into the consequences of mutations in various components of the splicing machinery as well as of cellular effects of spliceosome inhibition is a prerequisite to establish the role of splicing in tumor progression and treatment options, respectively.


Estimation of population pharmacokinetic parameters using destructively obtained experimental data: a simulation study of the one-compartment open model.
A simulation study of the one-compartment open pharmacokinetic model has been made. The population pharmacokinetic parameters which characterize the population of drug residues over time are assumed to be stochastic. A general theoretical model framework for parameter estimation via the method of extended least squares is presented. Formulas approximating the required mean and variance time functions are developed and subsequently used in the simulation study. The effects of four different designs in four different animal populations are presented. The simulated data are those of the single observation per animal per time point type. The characterizing population pharmacokinetic parameters have been analyzed for bias and reliability in both a naive and second-order mean model. Recommendations for choosing an appropriate sampling design are included.


Preparing students for interprofessional practice: exploring the intra-personal dimension.
The need for interprofessional education is now firmly embedded in undergraduate healthcare curricula frameworks in Northern Ireland and has a role to play in preparation for professional practice. A questionnaire determining students' "readiness" for interprofessional education has been widely used and reported in the literature but there are other factors that contribute to students' abilities to learn in an interprofessional context. Pre-qualification healthcare education can be viewed as having three inter-related components, intra-professional, interprofessional and intra-personal learning; the third of these underpinning the other two. Understanding more about personal learning needs can contribute to preparation for interprofessional interaction. A Studying and Learning Preferences Inventory (SALPI) was developed and validated for use with a range of healthcare professionals to assist in this process.


Celecoxib-induced erythema multiforme with glyburide cross-reactivity.
Erythema multiforme is an acute inflammatory skin reaction that often is caused by drugs, especially sulfonamides and their derivatives. Celecoxib, a cyclooxygenase-2 inhibitor, is a sulfonamide derivative commonly prescribed to treat arthritis in patients who cannot tolerate or who have a contraindication for taking traditional nonsteroidal antiinflammatory agents. A 57-year-old man with a previously undocumented sulfa allergy experienced an allergic skin reaction and had difficulty breathing secondary to throat swelling. His condition was believed to be erythema multiforme associated with the introduction of celecoxib into his drug regimen. His drug therapy was discontinued, but a subsequent reaction occurred when the sulfonamide derivative glyburide was reintroduced. It is important for clinicians to obtain a careful history and perform a thorough medical evaluation in all patients receiving sulfonamides and their derivatives, as a potentially life-threatening allergic reaction may be prevented.


[Effects of RNA interference targeting P2X7 receptor on microglial phagocytosis of amyloid-β protein].
To investigate the effect of silencing P2X7 receptor (P2X7R) by RNA interference on microglial phagocytosis of amyloid-β (Aβ) protein and to explore its possible mechanism. The small interfering RNA (siRNA) targeting the P2X7R gene was identified. The microglial cells activated by Aβ1-42 were infected with the Lipofectamine-siP2X7R and it was designated as siP2X7R group. Microglia infected with Lipofectamine-siNC was designated as siNC group and non-infected cells as con group. The levels of P2X7R mRNA were detected by real-time PCR and the P2X7R protein was determined by Western blotting. The levels of IL-1β and TNF-α were measured by ELISA. The microglial phagocytosis of Aβ1-42 was observed by ELISA and immunocytochemistry staining. Detected by the Real-time PCR, the expression level of P2X7R mRNA of siP2X7R group decreased significantly versus siNC and con groups (P<0.05). The lowered expression of P2X7R protein detected by Western blotting was consistent with Real-time PCR. After RNA interference silencing P2X7R, the levels of IL-1β and TNF-α detected by ELISA in siP2X7R group less than those in con, siNC groups, significantly (P<0.05). In con, siNC and siP2X7R groups respectively, the levels of Aβ1-42 in supernatant were (423±20) pg/ml, (417±16) pg/ml, (296±30) pg/ml and the levels of Aβ1-42 in the microglia were (190±37) pg/ml, (187±39) pg/ml, (322±26) pg/ml. Compared to siNC and con groups, in siP2X7R group the levels of Aβ1-42 in supernatant decreased (P<0.05) and the levels of Aβ1-42 in the microglia increased (P<0.05). Aβ1-42 immunofluorescence staining showed that the red fluorescent products were seen in the cytoplasm of most microglias in siP2X7R group, but in con or siNC groups in only few microglias these products were depicted. The silence expression of P2X7R by RNA interference effectively decreases the levels of IL-1β and TNF-α released by microglia and promotes microglia to phagocytose Aβ. P2X7R could be used as an effective therapeutic target for RNA interference treatment of Alzheimer's disease.


Pediatric selective IgM immunodeficiency.
Limited information exists on features of pediatric Selective IgM immunodeficiency (SIgMID). Previously published pediatric cases and 2 new cases are reviewed. English literature from PubMed and references from relevant articles were reviewed. Previously reported cases and 2 new cases from an allergy/immunology practice were analyzed. Forty-nine reported cases of SIgMID presented with respiratory infections (77.6%), gastrointestinal disease (16.3%), skin disease (12.2%), and meningitis (8.2%). Mean serum IgM level was 16.5+/-13.8 mg/dL. Two patients were identified with SIgMID among 6300 active pediatric patients (0.03%) presenting with asthma, vasomotor rhinitis, and recurrent respiratory infections. In the 51 cases reported, none developed lymphoproliferative disease nor evolved into panhypogammaglobulinemia; four fatalities were reported. The prevalence of SIgMID in our pediatric population was 0.03%. In general, respiratory infections are the common comorbid conditions. Death and autoimmune disease are uncommon complications of pediatric SIgMID.


The effect of using social pressure in cover letters to improve retention in a longitudinal health study: an embedded randomised controlled retention trial.
Retention of participants in cohort studies is important for validity. One way to promote retention is by sending a persuasive cover letter with surveys. The study aimed to compare the effectiveness of a covering letter containing social pressure with a standard covering letter on retention in a health cohort study. Social pressure involves persuading people to behave in a certain way by the promise that their actions will be made know to others. We implemented a mild form of social pressure, where the recipient was told that information about whether they responded to the current survey would be noted by the research team and printed on future correspondence from the research team to the recipient. The design was an embedded randomised controlled retention trial, conducted between July 2015 and April 2016 in Salford, UK. Participants in the host health cohort study were eligible. They received either: (1) a covering letter with two consecutive surveys (sent six and twelve months after recruitment), containing a social pressure intervention; or (2) a matching letter without the social pressure text. The primary outcome was retention in the host study, defined as return of both surveys. Randomisation was computer-generated, with stratification by household size. Participants were blinded to group assignment. Researchers were blinded for outcome ascertainment. Adults (n = 4447) aged over 65 years, with a long-term condition and enrolled in the host study, were randomly allocated to receive a social pressure covering letter (n = 2223) or control (n = 2224). All 4447 participants were included in the analysis. Both questionnaires were returned by 1577 participants (71%) sent the social pressure letters and 1511 (68%) sent control letters, a risk difference of 3 percentage points (adjusted odds ratio = 1.16 (95% confidence interval = 1.02-1.33)). A mild form of social pressure made a small but significant improvement in retention of older adults in a health cohort study. Investigation of social pressure across other research contexts and stronger social pressure messages is warranted. The host cohort study, the Comprehensive Longitudinal Assessment of Salford Integrated Care (CLASSIC) study is associated with the CLASSIC PROTECTs trial, which is registered on the ISRCTN registry. ISRCTN12286422 . Date of registration 19 June 2014.


Evidence-based symptom relief of intermittent claudication: efficacy and safety of cilostazol.
Intermittent claudication (IC) is a common, debilitating symptom of atherosclerotic peripheral arterial disease. There are two therapeutic objectives in patients with IC: relief of symptoms and secondary prevention of acute thrombotic complications. Among patients with Fontaine stage II disease, surgical revascularization for symptom relief is reserved for those in whom exercise/lifestyle modification and medical therapy has failed. To improve exercise tolerance in IC requires favourable alteration in the oxygen supply/demand relationship in the lower limb. Following the largest ever clinical trials programme in patients with IC, cilostazol, a phosophodiesterase III inhibitor, has been licensed for symptom relief in the UK. In double-blind, randomized, placebo-controlled trials involving over 2000 patients, cilostazol 100 mg b.d. produced significant and sustained improvements in pain-free and maximal walking distances as well as improved subjective assessments of quality of life. In particular, comparative studies with pentoxifylline (oxpentifylline) showed that cilostazol had significantly greater effects on functional outcome and exhibited good patient tolerance.


Molecular characterization of plasmids pS7a and pS7b from Lactococcus lactis subsp. lactis bv. diacetylactis S50 as a base for the construction of mobilizable cloning vectors.
Strain Lactococcus lactis subsp. lactis bv. diacetylactis S50 harbours five theta-replicating plasmids (pS6, pS7a, pS7b, pS80 and pS140). The aim of this study was to characterize domains involved in the replication and conjugative mobilization of the small plasmids pS7a and pS7b, which are structurally very similar. Complete nucleotide sequences of pS7a and pS7b were determined by cloning DNA fragments of different sizes into Escherichia coli vectors. Linearized plasmids and four EcoRI fragments of the pS7a and pS7b were cloned into an origin probe vector. Constructed plasmids (pSEV10, pSK10, pISE1a and pISE1b) were able to replicate in the strain L. lactis subsp. cremoris MG1363. In addition, experiments showed that plasmids pS7a and pS7b contained oriT sequences and their conjugative transfer directly depended on the presence of pS80 in donor cells. Plasmids pS7a and pS7b contained typical lactococcal theta replication origin and repB gene that enable them to replicate in the strain L. lactis subsp. cremoris MG1363. Plasmid pS80 plays a key role in the conjugative transfer of small plasmids. Plasmids pS7a and pS7b-based derivatives could be valuable tools for genetic manipulation, studying processes of plasmid maintenance and horizontal gene transfer in lactococci.


MAP4K4 Is a Threonine Kinase That Phosphorylates FARP1.
Mitogen-activated protein kinase 4 (MAP4K4) regulates the MEK kinase cascade and is implicated in cytoskeletal rearrangement and migration; however, identifying MAP4K4 substrates has remained a challenge. To ascertain MAP4K4-dependent phosphorylation events, we combined phosphoproteomic studies of MAP4K4 inhibition with in vitro assessment of its kinase specificity. We identified 235 phosphosites affected by MAP4K4 inhibition in cells and found that pTP and pSP motifs were predominant among them. In contrast, in vitro assessment of kinase specificity showed that MAP4K4 favors a pTL motif. We showed that MAP4K4 directly phosphorylates and coimmunoprecipitates with FERM, RhoGEF, and pleckstrin domain-containing protein 1 (FARP1). MAP4K4 inhibition in SH-SY5Y cells increases neurite outgrowth, a process known to involve FARP1. As FARP1 and MAP4K4 both contribute to cytoskeletal rearrangement, the results suggest that MAP4K4 exerts some of its effects on the cytoskeleton via phosphorylation of FARP1.


Towards personalized dementia care through meaningful activities supported by technology: A multisite qualitative study with care professionals.
Person-centred care is widely recognised as important for helping people with dementia maintain a sense of self and purpose in life - especially for those living in care facilities. Despite this, most care practices still adopt a medical approach in which physical needs are prioritized over psychosocial well-being. Addressing the need to find ways of promoting person-centred approaches in care, this study explored care professionals' reflections on a novel, technological intervention (SENSE-GARDEN) that combines multisensory stimuli and digital media to create personalized environments for people with dementia. The aim of this study was to explore the experiences of care professionals who had used SENSE-GARDEN for approximately 1 year. Three care homes in Norway, Belgium, and Portugal and 1 hospital in Romania used the SENSE-GARDEN with residents/patients with moderate to severe dementia over the course of 1 year. Qualitative data - including observations and interviews with 2 care professionals - were collected at the beginning of the study period from the Norwegian care home to explore initial impressions of the new SENSE-GARDEN room. At the end of the study period, 8 care professionals across the 4 facilities were interviewed for an in-depth exploration of their experiences. The two sets of data were analysed separately through reflexive thematic analysis. At the beginning of the study period, the staffs' focus was mainly on the novelty of the new SENSE-GARDEN room and how it provided opportunities for meaningful experiences. Post-intervention, the care professionals provided reflective accounts on how care could be delivered in alternative ways to standard practice. The themes generated from the post-intervention interviews were: "shifting focus onto personalized care", "building and fostering relationships", and "continuous discoveries". Through delivering person-centred care, the professionals reported a sense of purpose and achievement in their work. Professionals from care facilities across 4 different countries highlighted the value of interventions such as SENSE-GARDEN as a way of creating opportunities to better know people with dementia. Thus, they experienced improved relationships and greater job satisfaction. However, delivering person-centred interventions is time-consuming, and future research should evaluate the feasibility of sustaining them on a long-term basis.


[Innovation ability-driven optimization of the experimental teaching of human anatomy and animal physiology].
Innovation and entrepreneurship training through higher education sector is an important way to foster innovative talents and enhance their social adaptation abilities. We reformed and optimized the experimental teaching of human anatomy and animal physiology with the aim to promote the integration of students' theory learning with practice, to promote students' ability to apply anatomical and physiological knowledge to medicine, pharmacy, and life practice. Last but not least, students' innovative consciousness of applying scientific research to serve the society could also be enhanced. These practices would enhance the practical ability of the students through integrating the innovation education and professional education.


Interaction between stimulators of adenylate and guanylate cyclases in human leukocytes, platelets and arteries.
Buffered solutions (pH 5-pH 8) of glyceryl trinitrate (GTN), sodium nitroprusside (NaNP), S-nitroso-N-acetylpenicillamine (SNAP), molsidomine and its active metabolite (SIN-1) at concentrations of 30 microM were each tested at 37 degrees C for the release of nitric oxide (NO) by its co-oxidation to NO3 along with oxidation of oxyhaemoglobin to methaemoglobin. Apart from GTN and molsidomine, three other stimulators of guanylate cyclase released NO in a pH-dependent manner. Optimum for the release of NO by SIN-1 was at pH 7.4 and therefore this guanylate cyclase stimulator was chosen for studies on interaction with the adenylate cyclase stimulator iloprost, a stable prostacyclin analogue. Human platelets, neutrophils and strips of coronary arteries were used as targets to study this interaction. SIN-1 and iloprost synergized in the inhibition of collagen-induced platelet aggregation and protection of neutrophils against the release of lactate dehydrogenase, whereas no synergism between these drugs was observed in their vasorelaxant action. It is concluded that pharmacological synergism between adenylate and guanylate cyclase stimulators is not a general rule, but occurs only in certain types of cells.


Role of the PsbI protein in photosystem II assembly and repair in the cyanobacterium Synechocystis sp. PCC 6803.
The involvement of the PsbI protein in the assembly and repair of the photosystem II (PSII) complex has been studied in the cyanobacterium Synechocystis sp. PCC 6803. Analysis of PSII complexes in the wild-type strain showed that the PsbI protein was present in dimeric and monomeric core complexes, core complexes lacking CP43, and in reaction center complexes containing D1, D2, and cytochrome b-559. In addition, immunoprecipitation experiments and the use of a histidine-tagged derivative of PsbI have revealed the presence in the thylakoid membrane of assembly complexes containing PsbI and either the precursor or mature forms of D1. Analysis of PSII assembly in the psbI deletion mutant and in strains lacking PsbI together with other PSII subunits showed that PsbI was not required for formation of PSII reaction center complexes or core complexes, although levels of unassembled D1 were reduced in its absence. However, loss of PsbI led to a dramatic destabilization of CP43 binding within monomeric and dimeric PSII core complexes. Despite the close structural relationship between D1 and PsbI in the PSII complex, PsbI turned over much slower than D1, whereas high light-induced turnover of D1 was accelerated in the absence of PsbI. Overall, our results suggest that PsbI is an early assembly partner for D1 and that it plays a functional role in stabilizing the binding of CP43 in the PSII holoenzyme.


Methyl caffeate and some plant constituents inhibit age-related inflammation: effects on senescence-associated secretory phenotype (SASP) formation.
During aging, cells secrete molecules called senescence-associated secretory phenotype (SASP). They constitute chronic low-grade inflammation environment to adjacent cells and tissues. In order to find inhibiting agents of SASP formation, 113 plant constituents were incubated with BJ fibroblasts for 6 days after treatment with bleomycin. Several plant constituents showed considerable inhibition of IL-6 production, a representative SASP marker. These plant constituents included anthraquinones such as aurantio-obtusin, flavonoids including astragalin, iristectorigenin A, iristectorigenin B, linarin, lignans including lariciresinol 9-O-glucoside and eleutheroside E, phenylpropanoids such as caffeic acid and methyl caffeate, steroid (ophiopogonin), and others like centauroside, rhoifolin and scoparone. In particular, methyl caffeate down-regulated SASP factors such as IL-1α, IL-1β, IL-6, IL-8, GM-CSF, CXCL1, MCP-2, and MMP-3. Inhibition of these SASP mRNA expression levels also coincided with the reduction of IκBζ expression and NF-κB p65 activation without affecting the expression levels of senescence markers, p21 or pRb. Taken together, the present study demonstrated that methyl caffeate might be a specific and strong inhibitor of SASP production without affecting the aging process. Its action mechanisms involve the reduction of IκBζ expression and NF-κB p65 activation. Therefore, this compound might be effective in alleviating chronic low-grade inflammation linked to age-related degenerative disorders.


Transvenous extraction of an eight-year-old ventricular lead accidentally implanted into the left ventricle.
Incorrect implantation of a ventricular pacemaker (PM) lead into the left ventricle (LV) is a known problem associated with permanent pacing. The optimal management of such cases identified late has not been clearly established. Generally acceptable management options are: open-chest cardiac surgery using cardio-pulmonary bypass, chronic anticoagulation and antiplatelet-drugs therapy. Rarely, the problem is solved by percutaneous LV lead extraction. We present a case of a patient with DDD pacing and ventricular lead implanted incorrectly into the LV apex region via an atrial septal defect eight years ago. Chronic PM pocket infection developed after replacement of the device. Both leads were extracted percutaneously, and the embolic protection system (Filter-Wire EZ, Boston Scientific) was used to reduce cerebral circulation embolism. The hardest connective tissue adhesions affecting the lead and the anodal ring were found in the LV. Less dense surrounding fibrous tissue around the lead was present at all levels of the venous course of the lead and in the right atrium. Very small fragments of apparently connective tissue remnants were found in cerebral circulation protection filters, and had been removed after the procedure. We conclude that old, permanently implanted LV leads may be extracted percutaneously, especially when there is an increased risk of cardiac surgery, or where the patient's consent for surgical treatment is lacking. In order to perform the procedure it is recommended to establish a cerebral protection system and intraoperative transoesophageal echocardiography which are mandatory for successful lead removal.


Experimental method of transfer function linewidth determination for laser amplifiers using FM-to-AM conversion.
We propose an experimental method for the determination of the transfer function linewidth of a laser amplifier. This technique is based on a transfer function scan using frequency modulation to amplitude modulation (FM-to-AM) temporal modulation measurement as a function of wavelength. Using this method, we show that the output spectrum of a laser amplifier in Q-switch mode is not representative of the transfer function of the amplifier.


The emerging structure of vacuolar ATPases.
Bioenergetics and physiology of primary pumps have been revitalized by new insights into the mechanism of energizing biomembranes. Structural information is becoming available, and the three-dimensional structure of F-ATPase is being resolved. The growing understanding of the fundamental mechanism of energy coupling may revolutionize our view of biological processes. The F- and V-ATPases (vacuolar-type ATPase) exhibit a common mechanical design in which nucleotide-binding on the catalytic sector, through a cycle of conformation changes, drives the transmembrane passage of protons by turning a membrane-embedded rotor. This motor can run in forward or reverse directions, hydrolyzing ATP as it pumps protons uphill or creating ATP as protons flow downhill. In contrast to F-ATPases, whose primary function in eukaryotic cells is to form ATP at the expense of the proton-motive force (pmf), V-ATPases function exclusively as an ATP-dependent proton pump. The pmf generated by V-ATPases in organelles and membranes of eukaryotic cells is utilized as a driving force for numerous secondary transport processes. V- and F-ATPases have similar structure and mechanism of action, and several of their subunits evolved from common ancestors. Electron microscopy studies of V-ATPase revealed its general structure at low resolution. Recently, several structures of V-ATPase subunits, solved by X-ray crystallography with atomic resolution, were published. This, together with electron microscopy low-resolution maps of the whole complex, and biochemistry cross-linking experiments, allows construction of a structural model for a part of the complex that may be used as a working hypothesis for future research.


Effects of weightlessness in man.
The program for the Apollo 16 flight was designed to include both safeguards against and investigations of the physiological problems arising from increase in the period of manned space flight. Precautions included the provision of a controlled diet with high potassium content, carefully controlled work loads and work-rest cycles and an emergency cardiology consultation service, and investigations were made to enable pre-flight-post-flight comparisons of metabolic, cardiovascular and central nervous system data. Results of these investigations indicate that adjustment to weightlessness can be satisfactorily assisted by appropriate countermeasures including attention to diet.


Does Black Socioeconomic Mobility Explain Recent Progress Toward Black-White Residential Integration?
Studies of racial residential segregation have found that black-white segregation in U.S. metropolitan areas has declined slowly but steadily since the early 1970s. As of this writing, black-white residential segregation in the United States is approximately 25 % lower than it was in 1970. To identify the sources of this decline, we used individual-level, geocoded data from the Panel Study of Income Dynamics (PSID) to compare the residential attainment of different cohorts of blacks. We analyzed these data using Blinder-Oaxaca regression decomposition techniques that partition the decline in residential segregation among cohorts into the decline resulting from (1) changes in the social and economic characteristics of blacks and (2) changes in the association between blacks' social and economic characteristics and the level of residential segregation they experience. Our findings show that black cohorts entering adulthood prior to the civil rights movement of the 1960s experienced consistently high levels of residential segregation at middle age, but that cohorts transitioning to adulthood during and after this period of racial progress experienced significantly lower levels of residential segregation. We find that the decline in black-white residential segregation for these later cohorts reflects both their greater social and economic attainment and a strengthening of the association between socioeconomic characteristics and residential segregation. Educational gains for the post-civil rights era cohorts and improved access to integrated neighborhoods for high school graduates and college attendees in these later cohorts were the principal source of improved residential integration over this period.


Effective intraperitoneal antiprotease therapy for taurocholate-induced pancreatitis in rats.
In canine pancreatitis, irreversible hypotension and death follow saturation of the antiprotease molecules in peritoneal exudate by activated proteolytic enzymes which are released from the pancreas. This study has examined, in rats with taurocholate-induced pancreatitis, the efficacy of removal of the peritoneal exudate by aspiration and a single lavage, followed by instillation of an exogenous antiprotease solution. Instillation of human fresh frozen plasma, containing alpha 2-macroglobulin and alpha 1-antiprotease, was associated with the longest median survival. Aprotinin, although possessing a much greater trypsin inhibitory capacity, just failed to significantly improve the median survival time compared with the control group. Intraperitoneal antiprotease therapy is simple to perform, has a beneficial effect on survival time in this model and merits investigation in man.


The Microstructure Evolution and Formation Mechanism of Gradient Nanostructure Prepared on CrCoNi Medium-Entropy Alloy.
An equiatomic CrCoNi medium-entropy alloy was subjected to high-energy shot peening (HESP) to fabricate a gradient nanostructure (GNS) in this work. The microstructures of the GNS samples at different depths within the deformed layer were thoroughly investigated. The microstructure exhibited a transformation from unstressed coarse grains to deformed coarse grains, followed by the formation of ultrafine grains, and ultimately reaching a final nanocrystalline structure with a uniform size of approximately 50 nm. Detailed structural analysis indicated that the deformation process was primarily influenced by the interaction between dislocations and deformation twins, which was attributed to the low stacking fault energy (SFE) of the alloy. The nanocrystalline mechanism was divided into three stages. In the coarse-grained deformation stage, the dislocation band divided twin/matrix lamellae into sub-segments, and the cross twin divided coarse grains into ultrafine grains simultaneously. In the ultrafine grain deformation stage, dislocations were arranged around the deformation twins in order to break the twins to form incoherent boundaries, destroying the coherent relationship between the twin and matrix. Finally, in the nanocrystalline deformation stage, the nanocrystalline structure was further divided into smaller segments to accommodate additional strains through the interaction between dislocations and twins.


Safety of ultrasound-guided percutaneous renal biopsy-retrospective analysis of 1090 consecutive cases.
Ultrasound-guided renal biopsy with an automated spring-loaded biopsy device has become the standard method for kidney biopsy. Information on the success rate and safety of the routine use of this procedure from large series is not available. Such information is of interest for cost benefit considerations and for medicolegal purposes. We performed an audit of this procedure. From January 1993 to June 1997, 1090 percutaneous renal biopsies were performed in the renal units of Heidelberg (n = 557) and Karlsruhe (n = 533) using a spring-loaded biopsy device (Biopty; Radiplast AB, Uppsala, Sweden). After intensive local disinfection, biopsies were performed under local anaesthesia and direct visualization by ultrasound (Sonolayer SSH-140 A, Toshiba Inc., Japan). A puncturing adaptor was used (model UAGV 009 A, Toshiba, Japan). Of the 1090 biopsies 114 (10.4%) were performed on renal allografts and 976 (89.6%) on orthotopic kidneys. Biopsies were performed only if patients were strictly normotensive (<140/90 mmHg) and had normal coagulation parameters (PT, PTT, factor VIII, thrombocyte count, and bleeding time). All patients had been advised not to take aspirin or non-steroidal antiinflammatory agents for at least 5 days prior biopsy. We analysed (1) yield of diagnostically useful material, and (2) frequency of postbiopsy complications (e.g. macrohaematuria, haematoma, infections, and AV fistula). Except for one case requiring interventional radiology because of persisting blood loss and three cases requiring blood transfusions, no serious complications were seen in the 1090 consecutive renal biopsies, e.g. death, loss of kidney, life-threatening haemorrhage, or persisting haemodynamically relevant AV fistulae. The frequency of minor haematoma with an extension >2 x 2 cm, but no significant decrease of haemoglobin, was 2.2% (25/1090). Self-limited mild macrohaematuria occurred in 0.8% (9/1090). The incidence of small, haemodynamically irrelevant AV fistulae detected by Doppler ultrasound was 9% (48/533). Sufficient tissue for reliable histopathological diagnosis was obtained in almost all cases (1077/1090 = 98.8%). The median number of glomeruli per biopsy sample was 9 (range 1-37). If contraindications, especially high blood pressure and abnormal haemostasis, are respected, ultrasound-guided percutaneous renal biopsy with an automated biopsy device is safe. Skilled operators obtain satisfactory amounts of kidney tissue in almost all cases.


Matrix-dependent regulation of AKT in Hepsin-overexpressing PC3 prostate cancer cells.
The serine-protease hepsin is one of the most prominently overexpressed genes in human prostate carcinoma. Forced expression of the enzyme in mice prostates is associated with matrix degradation, invasive growth, and prostate cancer progression. Conversely, hepsin overexpression in metastatic prostate cancer cell lines was reported to induce cell cycle arrest and reduction of invasive growth in vitro. We used a system for doxycycline (dox)-inducible target gene expression in metastasis-derived PC3 cells to analyze the effects of hepsin in a quantitative manner. Loss of viability and adhesion correlated with hepsin expression levels during anchorage-dependent but not anchorage-independent growth. Full expression of hepsin led to cell death and detachment and was specifically associated with reduced phosphorylation of AKT at Ser(473), which was restored by growth on matrix derived from RWPE1 normal prostatic epithelial cells. In the chorioallantoic membrane xenograft model, hepsin overexpression in PC3 cells reduced the viability of tumors but did not suppress invasive growth. The data presented here provide evidence that elevated levels of hepsin interfere with cell adhesion and viability in the background of prostate cancer as well as other tissue types, the details of which depend on the microenvironment provided. Our findings suggest that overexpression of the enzyme in prostate carcinogenesis must be spatially and temporally restricted for the efficient development of tumors and metastases.


Breakdown of One-to-One Correspondence in Energy and Volume in a High-Pressure Heat-Treated Zr-Based Metallic Glass During Annealing.
The glassy state of a high-pressure heat-treated Zr50Cu40Al10 metallic glass was investigated from energetic and volumetric perspectives. The specific heat (Cp) data of initial heating and subsequent cooling from the supercooled liquid region indicates that the sample behaviour cannot be explained simply by the derivative of the well-known enthalpy (H)-temperature (T) curve. Unlike the Cp data, the thermal-expansion coefficient (α) value increased monotonically during the first heating step, which suggests the collapse of a one-to-one correspondence between the energy and volume during the process. The α data of the cooling process follow almost the same path as those of the as-cast process, whereas the corresponding Cp curves do not. This result implies that the volume appears to be more sensitive to obeying external heat compared with energy, which highlights the different time scale for achieving an equilibrium state in energy and volume. The second heating data of the Cp and α exhibit an inverse relationship against the corresponding first heating set, which confirms the breakdown of a one-to-one correspondence during annealing. The newly constructed energy-density diagram shows that the treated sample is rejuvenated volumetrically but is relaxed energetically during aging, which has never been observed experimentally previously.


Metabolic acidosis in hemodialysis: a neglected problem in Brazil.
Metabolic acidosis is associated with the high mortality seen in hemodialysis patients. The panorama of metabolic acidosis in hemodialysis in Brazil is unclear since 1996 when the analysis of bicarbonate levels was no longer a compulsory exam. We aimed to establish the prevalence of metabolic acidosis in a hemodialysis population and analyze the factors associated with low bicarbonate levels. A cross-sectional study was carried out to assess the prevalence of metabolic acidosis in adults undergoing regular hemodialysis from January to April 2017, in four dialysis centers from Niteroi, Rio de Janeiro, Brazil, and surroundings. For blood gas analysis, samples of 2 mL were collected in heparinized syringes before a midweek dialysis session. 384 patients with a mean age of 58.1 ± 15.8 years (54.5% men and 63.0%, non-white) were included. Approximately 30% had diabetes and 48%, hypertension. Nearly 88% used primary arteriovenous fistula as vascular access. The pre-dialysis mean serum tCO2 in the midweek session was 22.7 ± 3.0 mEq/L. The prevalence rate of serum bicarbonate below DOQI recommendation (22 mEq/L or higher) was 40.3%, and 6.5% had serum bicarbonate < 18 mEq/L. The dialyzer use count and the use of low-flux dialyzers were negatively associated whereas age and the standard Kt/V values were positively associated with the serum bicarbonate levels. The findings were in agreement with global data reported in previous studies. However, because the sample was relatively small and non-representative of the Brazilian population, a more comprehensive study, addressing national data is necessary to substantiate our findings.


The published trend of studies on COVID-19 and diabetes: bibliometric analysis.
Since the COVID-19 pandemic outbreak, diabetes mellitus (DM) has been at the core of the confirmed risk factors for fatal or critical care unit-treated COVID-19 and COVID-19 related complications. Although relevant studies on DM have developed rapidly during the COVID-19 pandemic. However, the aforementioned research results have not been systematically quantified by means of bibliometric analysis. The purpose of this study is to provide a comprehensive analysis of the current status and trends of publications related to DM research during the COVID19 epidemic. A bibliometric analysis was performed using the Web of Science database. In this study, we used citespace, R software and R-Bibliometrix to analyze keywords, most-cited authors, most-cited countries, most-cited global documents, and co-occurrence and co-citation networks. A total of 1688 publications was included in this study. Investigators from the United States contributed the most publications. The United States, China and Europe have the most collaboration with the other countries/regions. A total of 3355 institutions made contributions to this study. Of the top 10 institutions with the most publications, N8 Research Partnership showed the most centrality. Among the top 10 journals, Diabetes Research and Clinical Practice published the most articles. Among authors included, Khunti Kamlesh is rated first with 27 papers and has the highest centrality. The most frequently co-cited article is entitled "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The most popular keywords included diabetes, mortality, diabetes, outcome, occurrences, risk, and type 1 diabetes. This bibliometric study provides an overall picture of DM research and research trends during the COVID-19 pandemic and provides a basis for researchers to develop their next research strategies.


Coloring [Formula: see text]-Embeddable [Formula: see text]-Uniform Hypergraphs.
This paper extends the scenario of the Four Color Theorem in the following way. Let [Formula: see text] be the set of all [Formula: see text]-uniform hypergraphs that can be (linearly) embedded into [Formula: see text]. We investigate lower and upper bounds on the maximum (weak) chromatic number of hypergraphs in [Formula: see text]. For example, we can prove that for [Formula: see text] there are hypergraphs in [Formula: see text] on [Formula: see text] vertices whose chromatic number is [Formula: see text], whereas the chromatic number for [Formula: see text]-vertex hypergraphs in [Formula: see text] is bounded by [Formula: see text] for [Formula: see text].


Determination of saturated and unsaturated Fatty acids amount in leukocyte membranes from subjects fed with solid and fluid oils.
Modifications in dietary fatty acid intake might lead to a modification in membrane phospholipid fatty acid composition. The purpose of this study was to investigate relationship between different type of oil consumption and leukocyte membrane phospholipid composition. This study was carried out in subjects utilizing butter (n = 15), margarine (n = 15), fluid oil (n = 15) and mixed types of oils (n = 15) in total 60 subjects. Leukocytes were separated from total blood by dextran sedimentation method. Membrane lipids and proteins were isolated following the cell disruption. Fatty acids of membrane phospholipids were isolated by hydrolysation with phospholipase B under ultrasonic dismembranator. Free fatty acids were identified with gas chromatography at chloroform phase. The results obtained were compared with data obtained by chromatograms of the standards. Results more prominent values of arachidic, dihomo-gamma-linolenic and palmitoleic acids were found in butter-or mixed oil-user groups; eicosadienoic, eicosamonoenoic, dihomo-gamma-linolenic and behenic acids in fluid oil heptanoic, valeric, eicosadienoic and linolenic acids in margarine groups. The fatty acid composition of mixed oil; was similar to butter, while other two oils were so different. From this study, it was concluded that the type of oil consumption might have an influence on phospholipid components of plasma membranes.


Localization and concentration of a new bioactive acetic seminal fluid protein (aSFP) in bulls (Bos taurus).
The concentration of the new bioactive acetic seminal fluid protein (aSFP) was determined in body fluids of bulls. An aSFP-specific radioimmunoassay was elaborated and established for routine measurement. No crossreaction of the aSFP antibody was found with other seminal plasma proteins and known growth factors. The 14 kDa aSFP was detected in secretions of ampulla and seminal vesicles by immunoblot analysis, but not in testis, epididymis or blood. Large quantities of aSFP were measured by radioimmunoassay in the fluid from the ampulla (2.6 +/- 0.3 mg ml-1) and seminal vesicles (3.0 +/- 0.4 mg ml-1). Immunohistochemistry techniques demonstrated that aSFP was localized mainly in the secretory epithelium of ampulla and seminal vesicles. Large amounts of aSFP (4.0 +/- 0.4 mg ml-1) were present in seminal plasma of bulls within a range of 1-7 mg ml-1, but aSFP could not be found on membranes of spermatozoa. Concentrations vary considerably among individuals, suggesting that aSFP may have a role in bovine reproduction.


Size dependent chaperon properties of gold nanoparticles.
Citrate synthase is a heat labile enzyme showing a loss of activity even in response to a modest shift of temperature (35 degrees-45 degrees C). Gold nanoparticle is shown to prevent the thermal aggregation of this enzyme. The chaperon like activity of the nanoparticle diminishes if the particle size is reduced from 40 nm to 20 nm keeping the atomic concentration of gold constant. This implies that the effect is not merely due to enhanced surface area offered by the nano-surfaces. The effect is reversible as the protein separated out from nanoparticles behaves similar to control. The observed coupling between chaperon activity of the nanoparticle and its cluster forming ability is illustrated in terms of a thermal cage model.


Analysis of Free Legal Counselling for the Great East Japan Earthquake and the Outlook for the Field of Disaster Recovery and Revitalization Law.
Of the free legal counselling conducted by lawyers following the Great East Japan Earthquake, the results of analysis of approx. 40,000 cases have been disclosed by the Japan Federation of Bar Associations. These analysis results have been used as evidence serving as the basis for system revision and new legislation following the disaster, and have been of value to public policy, to a certain extent. In order to identify methods for realizing policy targets as know-how for public policy through the integration and analysis of legal needs in disaster areas, in FY2012 and thereafter, lectures on the "Disaster Recovery and Revitalization Law" were initiated by the Graduate School of Public Policy, Chuo University; Keio University Law School; and other institutions. Under the Disaster Recovery and Revitalization Law, new public policy education fusing various fields of government, policy, law, disaster prevention and crisis management, etc. has been implemented. By utilizing the database on free legal counselling, it may be possible to identify legal systems that need to be ironed out or problems related to public policy in preparation for a huge disaster such as an earthquake directly striking the Tokyo metropolitan area or an earthquake in the Nankai Trough. It is thought that intensifying study of relevant fields will result in the proposal of new designs in the fields of disaster prevention and crisis management.


Bactericidal efficacy of metronidazole against bacteria of human carious dentin in vitro.
The bactericidal efficacy of metronidazole against bacteria in carious dentin was clarified by measuring (1) the difference between bacterial recovery from suspensions of carious dentin on metronidazole-containing BHI-Blood agar plates (10 micrograms/ml) and control plates and (2) the difference between bacterial recovery from carious lesions of freshly extracted teeth, covered by alpha-tricalcium phosphate (TCP) cement containing metronidazole (5%) for 1-3 days and that covered by TCP only. More than 10(3) bacteria per milligram sample were recovered from carious dentin. More than 99% of the bacteria were, however, not recovered when samples were inoculated on metronidazole-containing BHI-Blood agar plates or when the lesions were covered by TCP cement containing metronidazole, indicating that metronidazole effectively disinfected the carious dentin.