The effects of interruption on squirrel monkey temporary threshold shift to a 96-hour noise exposure.
6 squirrel monkeys (Saimiri scuireus ) were exposed to an octave band of noise with a center frequency of 500 Hz under both continuous and interrupted conditions. Continuous exposures lasted for 4, 8, 16, 24, 48, 72 and 96 h, with complete recovery of hearing before the next exposure. The interrupted exposure was 96 h, long with 5-min interruptions so that temporary threshold shift (TTS) could be measured at 2, 4, 8, 12, 16, 24, 36, 48, 60, 72 and 84 h of exposure. There were no differences in TTS from 8 to 96 h of exposure between the two conditions. However, at 4 h of exposure, the interrupted exposure showed significantly less TTS (p less than 0.05) than the continuous exposure. The only difference between the exposures was a 5-min interruption at 2 h of exposure during the interrupted exposure. Thus, the interrupted-exposure method is valid for making generalizations about continuous exposures of 8 h or longer. The results also confirmed our previous finding that there was no asymptotic threshold shift for the squirrel monkey although we extended the exposure time to 96 h in this experiment. The similarity of human and squirrel monkey TTS growth functions is consistent with our earlier results and supports the suitability of the squirrel monkey as an animal model for noise-induced hearing loss in humans.


Simulation Study on Complex Conformations of Aβ42 Peptides on a GM1 Ganglioside-Containing Lipid Membrane.
Aggregation and complex formation of amyloid beta (Aβ) peptides on a neuronal cell membrane is a hallmark of neuro-disturbance diseases. In this work, we performed molecular dynamics (MD) simulations to investigate the initial stage of interactions of multiple Aβ42 peptides on a GM1 ganglioside-containing membrane that mimics a micro-domain on the neuronal cell surface. Conformational changes of Aβs due to adhesion on the membrane and subsequent molecular interactions among the Aβs were monitored. It was suggested from results of the two 1.0 µs simulation trials that stable complexes of Aβ peptides were not rapidly generated but that a steady binding of two Aβs was gradually formed. Observation of two Aβs that will be a complex with steady binding revealed that one Aβ was bound to the membrane surface, while the other was attached to the first one without strong contact with the membrane. The motion of the first one was restricted and its conformational change was limited, with the basic side-chains of Arg5 and Lys28 working as anchors to hold the Aβ helix region on the membrane. In contrast, the second one had high flexibility and showed diversity in its conformation. The second Aβ can search for an energetically favorable binding position on the first one. A parallel β-sheet structure was formed between the C-terminal sides of the two Aβs. Ala30 was critically important to lead the stable β-sheet conformation at the C-terminal hydrophobic domains of Aβs. In the N-terminal sides, helix structures were kept in both Aβs.


ASSESSMENT OF UNIVERSAL NEWBORN HEARING SCREENING AND INTERVENTION IN SHANGHAI, CHINA.
The aim of this study was to evaluate the universal newborn hearing screening (UNHS) and intervention program in Shanghai, China. This study included the quantitative analyses of the UNHS-Shanghai database in 2002-12 and qualitative assessment of the program. The Otoacoustic Emissions and the Automated Auditory Brainstem Evoked Responses tests were conducted in screening. The costs and benefits were calculated based on the number of participants in each stage. The short-term and long-term periods were defined as from birth to 15 years of age or to death (82-year-olds), respectively. Sensitivity analyses were conducted. A total 1,574,380 newborns were included, representing 93.6 percent of all eligible babies in Shanghai during the study period. The prevalence of newborn hearing loss was 1.66‰. The short-term/long-term program costs were ¥488.5 million (US$75.52 million)/¥1.08 billion (US$167.12 million), and the short-term/long-term program benefit was ¥980.1 million (US$151.53 million)/¥8.13 billion (US$1.26 billion). The program benefit was greater than its cost if the proportion of hearing-loss children enrolled in regular schools was no less than 41.4 percent of all hearing impaired children, as well as if the wage growth rate ranged from 3 percent to 8 percent. Qualitative results also suggested that stakeholders strongly supported this program. The universal newborn hearing screening and intervention program in Shanghai is justified in terms of the resource input in the long run, although there is still room for further improvement with respect to educational rehabilitation and a better infrastructure system.


Glucose consumption in recurrent gliomas.
In order to investigate the clinical significance of glucose consumption (GC) in recurrent gliomas, positron emission tomography with 18F-labeled fluorodeoxyglucose was measured in 18 cases of histologically verified recurrent gliomas. The GC of the tumors were categorized into four groups. Five tumors were in Group IV, the highest GC, four were in Group III, eight were in Group II, and one was in Group I. Masses in Groups III and IV were clearly defined as a hot spot higher than or similar to the GC of the contralateral cortex. Half of the recurrent gliomas showed the lower GC of Group I or II, but two thirds of these were histologically high-grade gliomas. Although GC in the recurrent gliomas did not always increase as expected, a focal increase of GC, even mild and small, in the area of previous surgery is diagnostically important. Tumors with high GC showed high histological malignancy, irrespective of tissue damage. Patients with tumors of low GC had longer survival rates than those with high GC, although statistical significance was not obtained. Thus, positron emission tomography with 18F-labeled fluorodeoxyglucose was useful for detecting the recurrence of gliomas and suggesting their histological malignancy and prognosis. Care should be taken because viable tumor cells could be present in areas of low GC and small recurrent masses could be missed because of the poor spatial resolution of positron emission tomography.


Comparison of methods to assess adherence to small-quantity lipid-based nutrient supplements (SQ-LNS) and dispersible tablets among young Burkinabé children participating in a community-based intervention trial.
Adherence to supplementation provided during an intervention trial can affect interpretation of study outcomes. We compared different approaches for estimating adherence to small-quantity lipid-based nutrient supplements (SQ-LNS) and dispersible tablets in a randomised clinical trial in Burkina Faso. A total of 2435 children (9-18 months) were randomly assigned to receive daily 20 g SQ-LNS with varying contents of zinc and a dispersible tablet containing 0 or 5 mg zinc. Adherence to SQ-LNS and tablets was assessed for all children through weekly caregiver interviews, and disappearance rate was calculated based on empty and unused packages returned during home visits. Additional adherence data were collected in different randomly selected subgroups of children: 12-h home observations were completed for children 11 and 16 months of age (n = 192) to assess consumption of SQ-LNS and dispersible tablets, and plasma zinc concentration was measured at baseline and 18 months (n = 310). Apparent adherence to SQ-LNS and dispersible tablets differed according to the assessment method used. Average daily caregiver-reported adherence to both SQ-LNS and dispersible tablets was 97 ± 6%. Disappearance rates showed similarly high average weekly adherence (98 ± 4%). In contrast, only 63% and 54% of children at 11 and 16 months, respectively, received SQ-LNS during the 12-h home observation periods, and fewer (32% and 27%) received a tablet. The lack of change in plasma zinc concentration after 9 months of supplementation suggests low adherence to the zinc tablet. Better methods are needed to assess adherence in community-based supplementation trials.


Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors.
Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 ± 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.


Quasiepitaxial Aluminum Film Nanostructure Optimization for Superconducting Quantum Electronic Devices.
In this paper, we develop fabrication technology and study aluminum films intended for superconducting quantum nanoelectronics using AFM, SEM, XRD, HRXRR. Two-temperature-step quasiepitaxial growth of Al on (111) Si substrate provides a preferentially (111)-oriented Al polycrystalline film and reduces outgrowth bumps, peak-to-peak roughness from 70 to 10 nm, and texture coefficient from 3.5 to 1.7, while increasing hardness from 5.4 to 16 GPa. Future progress in superconducting current density, stray capacitance, relaxation time, and noise requires a reduction in structural defect density and surface imperfections, which can be achieved by improving film quality using such quasiepitaxial growth techniques.


Shifting attitudes toward suicide over time: A latent profile analysis using the Korea National Suicide Survey.
South Korea has a high suicide rate, and changes in sociodemographic factors can further increase the rate. This study aims to (1) classify participants using the Attitudes toward Suicide Scale (ATTS) through latent profile analysis (LPA), (2) identify and compare the associations between sociodemographic factors with the ATTS in two survey years (2013, 2018), and (3) determine the moderating effect of survey year. Six sub-factors of the ATTS were used for LPA with a total of 2,973 participants. Sociodemographic characteristics were compared between groups, and multinomial logistic regression was conducted for each survey year. A moderation analysis was conducted with the survey year as moderator. LPA identified three groups of attitudes toward suicide: incomprehensible (10.3%), mixed (52.8%), and permissive (36.9%). The proportion of permissive attitudes increased from 2013 (32.3%) to 2018 (41.7%). Participants reporting suicidal behavior were more likely to be in the mixed and permissive groups than the incomprehensible group in both years. People reporting no religious beliefs were associated with the permissive group in the two survey years. The influence of education and income levels on groups differed by survey year. There were significant changes between 2013 and 2018 in attitudes toward suicide in the Korean population.


Various bacterial pathogens and symbionts infect the amoeba Dictyostelium discoideum.
The haploid soil amoeba Dictyostelium discoideum is a suitable model organism to study host-pathogen interactions with Legionella pneumophila. In this study we show that D. discoideum AX2 is also susceptible to infection with other important human pathogens and obligate intracellular symbionts. Infection assays demonstrated that Legionella-like amoebal pathogens (LLAP K62), Mycobacterium avium and the obligate intracellular endosymbionts of Acanthamoeba sp. strains TUME1, UWE25 and UWC6 were able to multiply within Dictyostelium. Salmonella typhimurium and Pseudomonas aeruginosa also invaded Dictyostelium, however were degraded shortly after uptake. Comitin-minus host cells were more permissive to infections with L. pneumophila and LLAP K62. Furthermore, this mutation significantly delayed the degradation of S. typhimurium. Accompanying electron and fluorescence microscopy of infected AX2 cells revealed that L. pneumophila and M. avium replicate within vacuoles, while LLAP K62, TUME1 and UWE25 were tightly enclosed by membranous structures within the cytoplasm. The beta-proteobacterium UWC6 was found to persist in the cytoplasm. The observed subcellular locations which correspond to the locations within the respective natural hosts suggest that D. discoideum is a representative model system for these pathogens and symbionts.


Long non-coding RNA Lucat1 is a poor prognostic factor and demonstrates malignant biological behavior in clear cell renal cell carcinoma.
Many long intergenic noncoding RNAs (lincRNAs) are encoded in the human genome. However, their biological functions, molecular mechanisms and prognostic values associated with clear cell renal cell carcinoma (ccRCC) have yet to be elucidated. We screened the lncRNAs' profile in ccRCC from The Cancer Genome Atlas (TCGA) database, and selected Lucat1 for further study. MTS, colony formation assay and transwell assay were performed to examine the effect of Lucat1 on proliferation and metastasis of ccRCC. The Chip and Rip assay was performed to verify that Lucat1 can bind to polycomb PRC2 complex and suppress p57 expression. In this study, we found that lncRNA Lucat1 expression was significantly up regulated in tumor tissues compared to matched adjacent non-tumor tissues. The Lucat1 expression level was also associated with grade, the clinical pathological stage and the survival time. Functional assays showed that Lucat1 can promote renal cancer cell proliferation in vitro and in vivo. Further analysis showed that Lucat1 can bind to polycomb PRC2 complex and suppress p57 expression. Taken together, our results suggest that Lucat1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for novel therapies in human ccRCC.


Copper pattern on self-assembled monolayer through microcontact printing.
Cu pattern on 3-mercaptopropyltrimethoxysilane self-assembled monolayers (MPTS-SAMs) modified glass substrate was achieved by a combination of hydrophobic treatment through microcontact printing, activation and electroless plating. The MPTS-SAMs modified glass substrate was selectively deactivated by microcontact printing 1-hexadecanethiol ethanol solution. X-ray photoelectron spectroscopy (XPS) and water contact angle measurements confirmed that a selectively deactivated pattern was obtained, which was attributed to the formation of disulfide linkages between MPTS and 1-hexadecanethiol. The substrate was selectively activated by dipping into Ag colloids solution and then applied for electroless Cu plating. XPS spectra suggested an ideal catalytic pattern on the substrate due to the deposition of Ag particles on the MPTS and the formation of S-Ag bonds. SEM showed that the microstructure of Cu pattern on MPTS-SAMs was in good agreement with the corresponding silicon master with a resolution of 10 microm. The average electrical resistivity was about 1.8 x 10(-6) omegacm, measured by four-point probe technique. The results suggested that microcontact printing deactivating reagents on SAMs is a potential technique for Cu patterns preparation.


Laboratory information management systems for DNA barcoding.
In the field of molecular biology, laboratory information management systems (LIMSs) have been created to track workflows through a process pipeline. For the purposes of DNA barcoding, this workflow involves tracking tissues through extraction, PCR, cycle sequencing, and consensus assembly. Importantly, a LIMS that serves the DNA barcoding community must link required elements for public submissions (e.g., primers, trace files) that are generated in the molecular lab with specimen metadata. Here, we demonstrate an example workflow of a specimen's entry into the LIMS database to the publishing of the specimen's genetic data to a public database using Geneious bioinformatics software. Throughout the process, the connections between steps in the workflow are maintained to facilitate post-processing annotation, structured reporting, and fully transparent edits to reduce subjectivity and increase repeatability.


Single-stranded DNA oligoaptamers: molecular recognition and LPS antagonism are length- and secondary structure-dependent.
In Gram-negative bacterial infection, lipopolysaccharide (LPS) readily overwhelms the host innate immune system, which could result in inflammation and sepsis in severe cases. Therefore, developing anti-LPS molecules would confer an efficient antibacterial strategy. We used SELEX (Systemic Evolution of Ligands by EXponential enrichment) to isolate single-stranded DNA (ssDNA) aptamers. By immobilizing and exposing different orientations of the LPS molecule on hydrophobic and hydrophilic surfaces, two populations of aptamers were captured from a library of 10(14-15) ssDNA oligonucleotides. Progressive SELEX enriched the aptamers towards thymidine residues. The more hydrophobic aptamers with T-rich loops showed strong molecular recognition for the lipid A moiety of LPS, binding at affinity of up to K(D) of 10(-9)M, and eliciting 95% neutralization of endotoxicity. The longer ssDNAs exhibited greater avidity for LPS and conferred more efficacious antagonism against LPS. The nucleotide composition imposes subtle influence on the aptamer folding and affinity for LPS.


The mouse mammary tumor virus long terminal repeat directs expression in epithelial and lymphoid cells of different tissues in transgenic mice.
A series of transgenic mice was developed that contained the simian virus 40 early region genes under the transcriptional control of the mouse mammary tumor virus long terminal repeat, including the promoter and glucocorticoid response elements. These mice all expressed the transgene in the epithelial cells of a number of different organs, such as lungs, kidneys, and prostate, salivary, and mammary glands, and in Leydig and lymphoid cells. Transcription of the chimeric gene was inducible by glucocorticoids, either after transfection into tissue culture cells or in cells cultured from animals carrying the transgene. Many, but not all, tissues which expressed the simian virus 40 sequences, as determined immunologically and by RNA analysis, developed into tumors, although they showed premalignant features. Since the mouse mammary tumor virus long terminal repeat is expressed in a number of different cell types when inherited through the germ line, the lactating mammary gland-specific transcription of endogenous proviruses must require other factors or sequences to achieve this specificity.


Effects of Dexmedetomidine Combined with Intravenous Anesthesia on Oxidative Stress Index, Postoperative Sleep Quality, and Brain Function in HICH Patients.
To investigate the effects of dexmedetomidine combined with intravenous anesthesia on oxidative emergency indicators, postoperative sleep quality, and brain function in patients with hypertensive cerebral hemorrhage (HICH), a total of 285 HICH patients admitted to our hospital from February 2020 to February 2021 were selected. The combined anesthesia group (n = 142) and the control group (n = 143) were established by the random number table method. The control group received conventional intravenous anesthesia, and the combined anesthesia group received dexmedetomidine combined intravenous anesthesia. Two groups of patients before and after operation was observed vital signs, oxidative stress index difference, comparing each time, the change of the two groups of brain function index, adverse reactions occurred between observation group, and the postoperative period of Pittsburgh Sleep Quality Index Scale (PSQI) score as a result, the Pearson correlation coefficient analysis of oxidative stress level and the correlation of HICH patients sleep quality. After operation, the mean arterial pressure (MAP) and heart rate (HR) of patients in both groups decreased significantly. The MAP level in the combined anesthesia group significantly increased compared to the control group, and the HR level decreased significantly than the control group (all P < 0.05). The levels of TNF-α, IL-6 and MDA in both groups increased significantly on day 7 after operation compared with before operation, but the indexes in the combined anesthesia group significantly decreased compared with the control group (P < 0.05). The level of superoxide dismutase (SOD) in both groups significantly decreased compared to that before operation, and the index value in combined anesthesia group significantly increased compared to that in the control group (P < 0.05). After surgery, the levels of central nerve specific protein (S100-β) and neuron specific enolase (NSE) in 2 groups increased with time, and the indexes in the combined anesthesia group significantly decreased compared to the control group (all P < 0.05). The incidence of adr in combined anesthesia group decreased significantly than that in control group (P < 0.05). After surgery, PSQI scores of the two groups showed a downward trend with time extension, and scores of the combined anesthesia group decreased significantly than those of the control group at 24 h, 48 h and 7 d after surgery (all P < 0.05). Pearson's correlation coefficient was used to analyze that TNF-α, IL-6, and MDA levels were positively correlated with PSQI score, while SOD level was negatively correlated with PSQI score (all P < 0.05). Dexmedetomidine combined with intravenous anesthesia can significantly improve the vital signs and oxidative stress response of HICH patients, effectively reduce the risk of adverse reactions, have little impact on the brain function of patients, and can improve the postoperative sleep quality of patients. This operation is worthy of clinical application. In addition, this study further analyzed the influence mechanism of postoperative sleep quality in patients with HICH and showed that TNF-α, IL-6, MDA, and SOD were all correlated with sleep quality in patients with HICH, suggesting that follow-up detection of these indicators has positive significance in improving the prognosis of patients.


Antigenic variability of different strains of Aspergillus fumigatus.
10 strains (isolates) of Aspergillus fumigatus, grown and harvested under identical conditions, were compared with respect to biochemical and immunological properties. The total protein and carbohydrate content isoelectric focusing pattern were determined for each of the individual strains. Their antigenic and allergenic activity was examined by a combination of crossed immunoelectrophoresis (CIE)/crossed radioimmunoelectrophoresis (CRIE) and RAST inhibition. Biochemical and immunochemical data indicated that considerable variation exists between the various isolates of A. fumigatus. 44 antigens were demonstrated in CIE of A. fumigatus, and 18 different allergens were identified in CRIE (2 major, 10 intermediate and 6 minor allergens).


Vasopressin administration facilitates fluid removal during hemodialysis.
Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.


Community pharmacy and NHS Direct in new team initiative.
Over the past five years, NHS Direct has handled over 18 million calls and become one of the world's principal providers of telephone-based health care advice. Research has shown that almost six per cent of callers seek advice about medicines and approximately 40 per cent of responses include advice about medicines. It was as a result of this identified need that the community pharmacy project was born. It has since been rolled out across all NHS Direct sites. The project aims to provide a framework to enable NHS Direct advisers to offer safe and appropriate information and referral.


Immune responses against Streptococcus pyogenes in human palatine tonsils.
We investigated cellular immunity against Streptococcus pyogenes in human tonsils by measuring antigen-specific immunoglobulin-secreting cells and the production of cytokines from CD4+ T cells in response to M proteins. The incidence of S pyogenes in tonsils was significantly higher in patients with recurrent tonsillitis (RT) than in patients with tonsillar hypertrophy (TH). M protein-specific immunoglobulin A (IgA) and immunoglobulin G spot-forming cells were increased in patients with RT compared with patients with TH. In RT the number of M protein-specific IgA spot-forming cells was significantly greater in the S pyogenes-negative subjects than in the S pyogenes-positive subjects. Proliferation of CD4+ T cells and production of interferon-gamma (IFN-gamma) and interleukins -2, -4, -5, and -6 (IL-2, IL-4, IL-5, and IL-6) from those T cells were observed in response to M protein. The concentrations of IFN-gamma and IL-4 were higher in RT than in TH. These findings suggest that S pyogenes is associated with the pathogenesis of RT and that immune responses against M protein may play an important role in preventing the colonization of this bacteria in tonsils.


Genetic and antigenic analysis of the influenza virus responsible for the 1992 Hong Kong equine influenza epizootic.
An outbreak of influenza occurred among thoroughbred racehorses in Hong Kong in November-December 1992, with morbidity of 37%. All horses involved had been vaccinated against equine-1 and equine-2 influenza viruses but not against the virus responsible for the 1989 equine influenza outbreak in northern China (influenza A/equine/Jilin/89, subtype H3N8). Therefore the source and nature of the virus causing the Hong Kong outbreak was investigated. Virus isolated from a horse infected during the outbreak was used for genetic analysis. All the viral gene segments were similar to those of equine-2 (H3N8) influenza viruses and unrelated to those of equine/Jilin/89 virus. The nucleotide sequence of the viral hemagglutinin gene showed high homology (99.4%) to that of influenza A/equine/Suffolk/89 (H3N8) virus which has circulated extensively in Europe. However, these viruses differed in their antigenic reactivity to a panel of monoclonal antibodies. Preliminary epizootiological information plus the concordance of amino acid sequence between hemagglutinins of the Hong Kong isolate and a contemporaneous equine-2 influenza virus isolate from the United Kingdom indicated that the probable source of the Hong Kong outbreak was horses recently imported from England or Ireland.


Evidence of radiation-induced reduction of height and body weight from repeated measurements of adults exposed in childhood to the atomic bombs.
Reduction of growth from exposure to atomic bomb radiation has been examined using individuals under 10 years old at the time of the bombing (ATB) and a growth curve analysis based on measurements of height and weight made in the course of the 4th-7th cycles of the Adult Health Study examinations (1964-1972). As expected, the largest difference in growth to emerge is between males and females. However, a highly significant reduction of growth associated with dose (DS86) was observed among those survivors for whom four repeated measurements of height and weight were available. Longitudinal analysis of a more extended data set (n = 821), using expected values based on simple linear regression models fitted to the three available sets of measurements of height and weight on the 254 individuals with a missing measurement, also indicates a significant radiation-related growth reduction. The possible contribution of such factors as poor nutrition and disruption of normal family life in the years immediately after the war is difficult to evaluate, but the effects of socioeconomic factors on the analysis of these data are discussed.


Equation for calculating the concentration of solvent in air that discriminates between exposure and non-exposure based on biomarker concentrations in the urine of workers.
To develop a new method for evaluating the intensity of workers. exposures to toluene alone or toluene in mixed solvents, regression equations were calculated between the concentrations of toluene to which workers were exposed and the concentrations of hippuric acid or toluene in workers. urine samples taken at the end of their shifts. Thereafter, the discriminant exposure concentration of the solvents in air, which was the concentration considered to discriminate exposure from non-exposure within a fixed level of error using fiducial ranges of individual specimens (DEC-I) or using confidence ranges of regression equation (DEC-R), was measured by a scale. The devised equations were applied to calculate DEC-I or DEC-R accurately using the formulas expressing a regression line and its fiducial ranges or confidence ranges. The equations can calculate not only more precise values of DEC-I or DEC-R than can be measured by a scale, but can also calculate values corresponding to any level of error. Moreover, DEC-I and DEC-R can be defined by the equations. The concentration capable of discriminating TLV (threshold limit value) exposure from non-TLV exposure was estimated using fiducial ranges (DTL-I) and then using confidence ranges of the regression equation (DTL-R).


Treatment of hemorrhagic periodontitis using neopredin.
Thirty hemorrhagic periodontitis adult patients completed a 90-day controlled clinical study to determine the clinical effects of the antiinflammatory preparation neopredin gel containing prednisolone, neomycin sulfate and chlorhexidine when used an adjunct to scaling and root planing. The results were evaluated using the Quigley-Hein plaque index, the Schour-Massler gingival bleeding index, the Svrakov-Pissarev gingival vital staining index, the Muleman-Son sulcus bleeding index and the percentage of bleeding on probing sites. Treatment with neopredin resulted in consistently lower values of the mean plaque index score, the gingival bleeding index score, the vital staining index score and the sulcus bleeding index score at days 14.30 and 90. A significant reduction in the mean pocket probing depth was observed at day 30. The first symptoms of recurrent gingival inflammation were noticed at day 90. Our results indicate that neopredin is effective in reducing supragingival plaque accumulation, gingival inflammation, bleeding on probing and periodontal pocket depth and these reductions are highly significant.


Identification of possible nutritional and stress risk factors in the development of marmoset wasting syndrome.
Marmoset wasting syndrome (MWS) describes a series of symptoms in callitrichids that lead to general weakness and a failure to thrive in captive conditions such as zoological institutions. Though the cause of MWS has not been identified, the majority of hypotheses are linked to deficiencies of specific nutrients and increased stress levels. Questionnaires were sent to zoos requesting information on diets and housing of currently living and dead callitrichids before their deaths, as well as their postmortem reports. Risk factors for development and occurrence of MWS include close proximity of predator enclosures and high levels of dietary magnesium and zinc. Variables with effects which may protect against the development of MWS included provision of a nest box, natural trees within enclosure, reduced visibility to visitors, as well as dietary factors such as higher concentrations of potassium and fiber fractions. The protective effects of limited concentrate feeds and increased total dietary fiber may help reduce the risks of developing MWS. The minerals may not have biological implications in MWS per se, however, they may be reflective of diets too high in concentrates and too low in plant matter. Habitat designs that are less naturalistic and those which provide insufficient privacy or hide areas may increase chronic stress for callitrichid species, possibly because of visitor-related stress. Other causes of chronic stress in captive zoo populations should be the topic of further research to reduce occurrence of MWS.


Study on community Tai Chi Chuan participants' leisure benefits and well-being: Using Taoyuan City as an example.
The aim of this study was to discuss the Research of Community Tai Chi Chuan Participants' Leisure Benefits and Well-being. A questionnaire survey was conducted on the community Tai Chi Chuan participants in Taoyuan city. A total of 500 valid questionnaires were retrieved, and the data were analyzed with SPSS 12.0 and AMOS 7.0 structural equation model analysis (SEM). The findings were as followed: 1) The background variables of the community Tai Chi Chuan participants in Taoyuan City: Gender had no difference in the factor of ``psychological benefit'' of leisure benefits. Occupation, age, education, the number of times a week to participate community Tai Chi Chuan and participation in seniority reached significant difference in leisure benefits. 2) The background variables of the community Tai Chi Chuan participants in Taoyuan City: gender, occupation, age, education, the number of times a week to participate community Tai Chi Chuan, participation in seniority reached significant difference in well-being. 3) The study showed community Tai Chi Chuan participants' leisure benefits had a significant positive correlation in well-being. Based on the findings, suggestions were proposed to related Taiwan Tai Chi Chuan promotion for reference.


Studies of aquatic fungi. XIX. Aquatic fungi of the Rudawka River.
Studies of aquatic fungi were carried out in the annual cycle in the years 1987-1989 against a background of hydrochemical relations in the Rudawka River, a tributary of the Orlanka. 35 species of aquatic fungi were found, of which a prevailing number were reported many times in various water reservoirs. Such species, however, as Olpidium entophytum, Achlyogeton entophytum, Rhizidium verrucosum, Catenaria sphaerocarpa, Leptolegniella keratinophila and Zoophagus tentaclum are new to Polish hydromycoflora. In summer months (July-August) the mycoflora of this river was poor, the occurrence of various species of aquatic fungi increased in autumn and spring, and less so in winter.


Enabling people with intellectual and other disabilities to make verbal requests using cardboard chips with mini objects or pictures and a smartphone.
This study aimed to help six participants with intellectual disability combined with sensory and motor impairments to make verbal requests through the use of a technology system involving cardboard chips and a smartphone. The participants were divided into two groups of three based on whether they did or did not have visual skills. Each group was exposed to the intervention with the technology system according to a non-concurrent multiple baseline across participants design. During the 20 min intervention sessions, the participants were provided with a smartphone and nine cardboard chips each of which had a picture or object (i.e., a mini object replica or raised object contour) and several radio frequency identification tags attached to it. To make a request, the participants were to bring a cardboard chip in contact with the smartphone. This read the tags attached to the cardboard and verbalized the request related to that cardboard. During the baseline (without cardboard chips and smartphone), the participants' mean frequency of independent requests (all non-verbal requests) varied between zero and near 1.5 per session. During the intervention (with cardboard chips and smartphone), the participants' mean frequency of independent requests (all verbal requests) varied between over 4.5 and about 10 per session. The results suggest that the system might be useful to help participants like the ones included in this study to make verbal requests with simple responses.


Finding a periodic attractor of a Boolean network.
In this paper, we study the problem of finding a periodic attractor of a Boolean network (BN), which arises in computational systems biology and is known to be NP-hard. Since a general case is quite hard to solve, we consider special but biologically important subclasses of BNs. For finding an attractor of period 2 of a BN consisting of n OR functions of positive literals, we present a polynomial time algorithm. For finding an attractor of period 2 of a BN consisting of n AND/OR functions of literals, we present an O(1:985(n)) time algorithm. For finding an attractor of a fixed period of a BN consisting of n nested canalyzing functions and having constant treewidth w, we present an O(n(2p(w+1))poly(n)) time algorithm.


Modern stroke unit.
The modern stroke unit is making significant contributions to the care of stroke victims and is proving to be an effective, cost-saving enterprise. The precise factors that contribute to the efficacy of these units have yet to be identified, but a combination of protocolized approaches to patient care, critical paths, a focus of expertise, and heightened index of suspicion for comorbidities all probably play a role. This article outlines the basic features of a modern stroke unit and surveys the literature on stroke unit outcomes.


Matching evaluation between occupational contact dermatitis and various jobs in Yazd in during 2007-2012.
Skin disorders comprise more than 35% of all occupationally related diseases. 90-95% of work-related dermatoses are contact dermatitis. Effects of occupational dermatitis in the lives of workers are substantial. To plan any preventive program we need basic statistics of the problem, that we had no reliable one which includes a lot of industries in Iran. Therefore we decided to determine occupational contact dermatitis, and it's subtypes prevalence in various jobs. The objective of this study is determination of occupational contact dermatitis, and it's subtypes prevalence and comparison among various jobs. In this cross -sectional study, we examined 3061 workers of various industries during 2007-2012 and recognized contact dermatitis cases. Irritant and allergic cases were separated according to clinical judgment of physician and patch test using European standard series. We found 271 (prevalence=8.8%) occupational contact dermatitis cases which 247 (91.1%) were irritant, and the rest were allergic. The highest prevalence was in washing powder production and then glaze and paint workers, mechanists and chemical workers were located. There is a great variability for occupational contact dermatitis in various industries and between different countries. These statistics changes during the time by changing in number of workers and their characteristics, variation in material and process and glove use situation. So every country must have a national data bank of occupational contact dermatitis, which must be updated after a period of time.


Rosuvastatin promotes benefits on induced periodontitis in hypertensive rats.
The potential benefits of statins in modulating periodontal disease is supported by in vitro and clinical studies showing statins can induce a lower expression of proinflammatory cytokines and matrix metalloproteinases. The aim of this study was to evaluate the effects of rosuvastatin (ST) on ligature-induced periodontitis in spontaneously hypertensive rats (SHR). Fifty-four adult male rats were divided into three groups: SHR-C, SHR-L and SHR-L-ST (C, control; L, ligature groups). In the SHR-L-ST group, animals were treated with daily 2 mg/kg ST administration. In L groups, a ligature remained around mandibular first molars for 10 d. Each group was divided for killing at 10 or 21 d postoperatively. Microtomographic and histometric analyses were performed. Osteoclastogenesis was evaluated by tartrate-resistant acid phosphatase assay and gene expression of 84 proinflammatory mediators by polymerase chain reaction array. The SHR-L-ST group showed reduced bone loss and attachment loss in comparison with the SHR-L group at both 10 and 21 d postoperatively (p < 0.05). ST decreased the amount of tartrate-resistant acid phosphatase-positive cells compared with the SHR-L group at both 10 and 21 d (p < 0.05). The SHR-L-ST group presented 14 genes differentially expressed when compared with SHR-L group, featuring a downregulated gene profile at 10 d. Statin therapy may promote a protective effect against alveolar bone and connective tissue attachment losses attributable to periodontitis in hypertensive rats through inflammatory gene profile modulation.


Next-generation sequencing reveals germline mutations in an infant with synchronous occurrence of nephro- and neuroblastoma.
Although neuro- and nephroblastoma are common solid tumors in children, the simultaneous occurrence is very rare and is often associated with syndromes. Here, we present a unique case of synchronous occurrence of neuro- and nephroblastoma in an infant with no signs of congenital anomalies or a syndrome. We performed genetic testing for possible candidate genes as underlying mutation using the next-generation sequencing (NGS) approach to target 94 genes and 284 single-nucleotide polymorphisms (SNPs) involved in cancer. We uncovered a novel heterozygous germline missense mutation p.F58L (c.172T→C) in the anaplastic lymphoma kinase (ALK) gene and one novel heterozygous rearrangement Q418Hfs(*)11 (c.1254_1264delins TTACTTAGTACAAGAACTG) in the Fanconi anemia gene FANCD2 leading to a truncated protein. Besides, several SNPs associated with the occurrence of neuroblastoma and/or nephroblastoma or multiple primary tumors were identified. The next-generation sequencing approach might in the future be useful not only in understanding tumor etiology but also in recognizing new genetic markers and targets for future personalized therapy.


Gabor filters and phase portraits for the detection of architectural distortion in mammograms.
Architectural distortion is a subtle abnormality in mammograms, and a source of overlooking errors by radiologists. Computer-aided diagnosis (CAD) techniques can improve the performance of radiologists in detecting masses and calcifications; however, most CAD systems have not been designed to detect architectural distortion. We present a new method to detect and localise architectural distortion by analysing the oriented texture in mammograms. A bank of Gabor filters is used to obtain the orientation field of the given mammogram. The curvilinear structures (CLS) of interest (spicules and fibrous tissue) are separated from confounding structures (pectoral muscle edge, parenchymal tissue edges, breast boundary, and noise). The selected core CLS pixels and the orientation field are filtered and downsampled, to reduce noise and also to reduce the computational effort required by the subsequent methods. The downsampled orientation field is analysed to produce three phase portrait maps: node, saddle, and spiral. The node map is further analysed in order to detect the sites of architectural distortion. The method was tested with 19 mammograms containing architectural distortion. In a preliminary experiment, a sensitivity of 84% was obtained at 7.8 false positives per image.


Effects of micronization on the physico-chemical properties of peels of three root and tuber crops.
The aim of this study was to investigate the effect of micronization on the physicochemical properties of the peels of root and tuber crops, including yam (Dioscorea alata L.), taro (Colocasia esculenta L.) and sweet potato (Ipomea batatas L.). Two continuous milling sections, including hammer milling and ball milling, were applied to three samples to obtain micro-sized particles of root and tuber peels. The micronization by ball-milling treatment for 10 h was carried out to investigate the distribution of particle sizes and the changes in physiochemical properties. The results indicate that the peels of three crops appeared to be significantly decreased in particle size after 10 h of ball-milling treatment. Moreover, the ball-milling treatments resulted in the redistribution of fiber components from insoluble fiber to soluble fiber. The micronization treatments decreased the bulk density but increased the solubility and water-holding capacities of the micronized peels. Our findings suggested that micronization treatments can improve functional properties of the fiber components of micronized peels, which provide a good source of dietary fiber in food applications.


[Psychotherapies for the Treatment of Phantom Limb Pain].
The phantom limb pain has been described as a condition in which patients experience a feeling of itching, spasm or pain in a limb or body part that has been previously amputated. Such pain can be induced by a conflict between the representation of the visual and proprioceptive feedback of the previously healthy limb. The phantom limb pain occurs in at least 42 to 90% of amputees. Regular drug treatment of phantom limb pain is almost never effective. A systematic review of the literature was conducted in Medline and Cochrane using the MESH terms "phantom limb pain" and "psychotherapy", published in the last 10 years, in English and Spanish, finding 49 items. After reviewing the abstracts, 25 articles were excluded for not being related to the objective of the research. Additionally cross references of included articles and literature were reviewed. To describe the psychotherapies used in the management of phantom limb pain, their effectiveness and clinical application reported in the literature. The mechanisms underlying phantom limb pain were initially explained, as were the published studies on the usefulness of some psychotherapies such as mirror visual feedback and immersive virtual reality, visual imagery, desensitization and reprocessing eye movements and hypnosis. The phantom limb pain is a complex syndrome that requires pharmacological and psychotherapeutic intervention. The psychotherapies that have been used the most as adjuvants in the treatment of phantom limb pain are mirror visual feedback, desensitization and reprocessing eye movements, imagery and hypnosis. Studies with more representative samples, specifically randomized trials are required.


Mitochondrial COI and 16sRNA evidence for a single species hypothesis of E. vitis, J. formosana and E. onukii in East Asia.
Tea green leafhopper is one of the most damaging tea pests in main tea production regions of East Asia. For lack of recognized morphological characters, the dominant species of tea green leafhoppers in Mainland China, Taiwan and Japan have always been named as Empoasca vitis Göthe, Jacobiasca formosana Paoli and Empoasca onukii MATSUDA, respectively. Furthermore, nothing is known about the genetic relationships among them. In this study, we collected six populations from Mainland China, four populations from Japan and one population from Taiwan, and examined the genetic distances in the COI and 16sRNA regions of mtDNA among them. The results showed that the genetic distances based on single gene or the combined sequences among eleven leafhopper populations were 0.3-1.2%, which were all less than the species boundary of 2%. Moreover, there were at least two haplotypes shared by two distinct populations from different regions. The phylogenetic analysis based on single gene or combined sets also supported that tea green leafhoppers from Mainland China, Taiwan and Japan were closely related to each other, and there were at least two specimens from different regions clustered ahead of those from the same region. Therefore, we propose that the view of recognizing the dominant species of tea green leafhoppers in three adjacent tea production regions of East Asia as different species is unreliable or questionable and suggest that they are a single species.


Persisting improvement in complaint-related cognitions initiated during medical consultations in functional abdominal complaints.
Previously it was shown that during a series of out-patient consultations dysfunctional complaint-related cognitions and anxiety diminished significantly in patients with functional abdominal complaints (IBS). The aim of the present study was to assess the maintenance of positive changes initiated during medical consultations in the patients' complaint-related cognitions and anxiety, as well as the influence of these cognitions on the severity of the complaints, 6 months after the first visit to the out-patient clinic. One hundred and five consecutive patients with IBS referred by their general practitioners to the out-patient clinic for internal medicine completed questionnaires about their complaints and their complaint-related cognitions and anxiety before the first and after the last out-patient visit and again at follow-up, 6 months after the first out-patient consultation. Positive changes in the patients' complaint-related cognitions during the consulting period were found to persist during the follow-up period. Improvement in abdominal complaints at follow-up was found to be related to the level of the patients' state anxiety, fear of cancer, and catastrophizing cognitions at the last out-patient visit. Medical consultations can bring about long-lasting positive changes in prognostically unfavourable cognitions and anxiety. These changes appear to be related to a better outcome of IBS.


[Regulatory peptides in system mechanisms of goal-directed behavior: experience of physiological activity study].
The paper presents some new data and original approaches to study of the role of opioid and vasoactive peptides in the integrative functioning of the brain. The authors performed a comparative analysis of the physiological activity of native and complex (combined with protein) forms of these biologically active substances, and discuss a possible role of autoimmune processes in peptide self-regulation of goal-directed behavior.


ProDisc artificial total lumbar disc replacement: introduction and early results from the United States clinical trial.
Multicenter prospective randomized study of artificial disc replacement (ProDisc) versus circumferential fusion (standard of care) for one- and two-level degenerative disc disease. This is an interim analysis on patients seen at the Spine Institute Saint John's Health Center, Santa Monica, California. To evaluate early pain and functional outcomes of patients treated with disc replacement or fusion and to assess the capacity of this intervertebral disc replacement for preserving motion in the lumbar spine. Disc replacement is intended to reduce pain via removal of the diseased disc while restoring physiologic motion and height at the affected level. The long-term physiologic advantage of disc replacement to fusion is that preservation of motion may prevent additional degeneration at adjacent levels. Patients meeting inclusion criteria were consented for study. Randomization was performed using a 2 to 1 ratio of disc replacement procedure to a fusion procedure. Patients rated their pain on the Visual Analogue Scale and completed the Oswestry Disability Index questionnaire. Radiographs were taken. Assessments were made before surgery and after surgery at 6 weeks, 3 months, 6 months, and 1 year (ongoing). Changes from preoperative pain, disability, or motion were separately evaluated as a function of treatment using repeated measures mixed design analysis of variance. This analysis includes data up to 6 months from the first 53 randomized patients. There were 35 patients who underwent disc replacements, and 18 patients had fusion procedures. Disc replacement patients had a significant reduction in pain and disability at earlier evaluations. By 6 months, the relative improvement on both the Visual Analogue Scale and Oswestry (both, P < 0.05) were similar for disc replacement and fusion patients. Greater motion was found at L4-L5 for disc replacement patients (P < 0.05) than fusion patients. A similar trend was noted at L5-S1 (P was not significant). Disc replacement patients reported significantly less pain (Visual Analogue Scale) and disability (Oswestry) in the early period following surgery compared to fusion patients. This difference disappeared by 6 months. When compared to fusion, the disc replacement allowed preservation of motion at L4-L5 with a similar trend at L5-S1.


IL-5 and its receptor: which role do they play in the immune response?
IL-5 is a homodimeric glycoprotein that promotes proliferation and differentiation of activated B cells, and controls the production and functions of some other hematopoietic cells, such as Ly-1(CD5)+ B cells, eosinophils and basophils. In humans, IL-5 acts as a differentiation and growth factor for eosinophils, and is the major cytokine involved in the production of eosinophilia. IL-5 acts on its target cells through the specific receptor that is composed of two polypeptide chains, a and b. The alpha-chain is unique to IL-5, while the beta-chain is common to IL-5 receptor, IL-3 receptor and granulocyte-macrophage colony stimulating factor (GM-CSF) receptor.


Intimal proliferation of cerebral arteries after subarachnoid blood injection in pigs.
A model of experimental subarachnoid hemorrhage in young pigs has been created using two subarachnoid blood injections. Cerebral arteries of the pig demonstrate intimal proliferation and medial necrosis 10 days after experimental blood injection; this appears to be a reaction to arterial injury. The similarity between the arterial reaction to subarachnoid blood and the general process of atherosclerosis is noted, and steps have been taken to insure that the vasculopathy described is truly a response to the injected blood. The authors conclude that the intimal proliferation observed between 1 and 2 weeks after experimental subarachnoid blood injection is an indicator of arterial injury and is, therefore, a good end point for further studies.


Severity of Chronic Graft-versus-Host Disease and Late Effects Following Allogeneic Hematopoietic Cell Transplantation for Adults with Hematologic Malignancy.
The study aimed to determine the association of chronic graft-versus-host disease (cGVHD) diagnosis and severity with the development of subsequent neoplasms (SN) and nonmalignant late effects (NM-LE) in 2-year disease-free adult survivors following hematopoietic cell transplantation (HCT) for a hematologic malignancy. To do so, we conducted a retrospective analysis of 3884 survivors of HCT for hematologic malignancy in the Center of International Blood and Marrow Transplant Research database. We conducted a landmark analysis at the 2-year post-transplantation date, comparing first SN and NM-LE in survivors with and without cGVHD. The cumulative incidence (CuI) of SN and NM-LE were estimated through 10 years post-HCT in both groups, with death or disease relapse as a competing risk. Cox proportional hazards models were used to evaluate the associations of cGVHD and its related characteristics with the development of SN and NM-LE. The estimated 10-year CuI of SN in patients with GVHD (n = 2669) and patients without cGVHD (n = 1215) was 15% (95% confidence interval [CI], 14% to 17%) versus 9% (7.2% to 11%) (P < .001). cGVHD by 2 years post-HCT was independently associated with SN (hazard ratio [HR], 1.94; 95% CI, 1.53 to 2.46; P < .0001) with a standardized incidence ratio of 3.2 (95% CI, 2.9 to 3.5; P < .0001). Increasing severity of cGVHD was associated with an increased risk of SN. The estimated 10-year CuI of first NM-LE in patients with and without cGVHD was 28 (95% CI, 26% to 30%) versus 13% (95% CI, 11% to 15%) (P < .001). cGVHD by 2 years post-HCT was independently associated with NM-LE (HR, 2.23; 95% CI, 1.81 to 2.76; P < .0001). Multivariate analysis of cGVHD-related factors showed that increasing severity of cGVHD, extensive grade, having both mucocutaneous and visceral involvement, and receiving cGVHD treatment for >12 months were associated with the greatest magnitude of risk for NM-LE. cGVHD was closely associated with both SN and NM-LE in adult survivors of HCT for hematologic malignancy. Patients identified as having more severe involvement and both mucocutaneous and visceral organ involvement may warrant enhanced monitoring and screening for SNs and NM-LEs. However, caution is warranted when interpreting these results, as patients with cGVHD may have more vigilant post-transplantation health care and surveillance for late effects.


The Paradoxical Leishmanicidal Effects of Superoxide Dismutase (SOD)-Mimetic Tempol in Leishmania braziliensis Infection in vitro.
Leishmaniasis is an infectious disease caused by protozoans of the genus Leishmania. The macrophage is the resident cell in which the parasite replicates and it is important to identify new compounds that can aid in parasite elimination since the drugs used to treat leishmaniasis are toxic and present side effects. We have previously shown that treatment of Leishmania braziliensis-infected macrophages with DETC (Diethyldithiocarbamate) induces parasite killing, in vivo. Thus, the objective of this study was to further evaluate the effect of oxidants and antioxidants in L. braziliensis-infected macrophages, following treatment with either oxidizing Hydrogen Peroxide, Menadione, DETC, or antioxidant [NAC (N-Acetyl-Cyteine), Apocynin, and Tempol] compounds. We determined the percentage of infected macrophages and number of amastigotes. Promastigote survival was also evaluated. Both DETC (SOD-inhibitor) and Tempol (SOD-mimetic) decreased the percentage of infected cells and parasite load. Hydrogen peroxide did not interfere with parasite burden, while superoxide-generator Menadione had a reducing effect. On the other hand, NAC (GSH-replenisher) and Apocynin (NADPH-oxidase inhibitor) increased parasite burden. Tempol surfaces as an interesting candidate for the chemotherapy of CL with an IC50 of 0.66 ± 0.08 mM and selectivity index of 151. While it remains obscure how a SOD-mimetic may induce leishmanicidal effects, we suggest the possibility of developing Tempol-based topical applications for the treatment of cutaneous leishmaniasis caused by L. braziliensis.


Effect of positive end-expiratory-pressure on regional ventilation in patients with acute lung injury evaluated by electrical impedance tomography.
For the treatment of patients with adult respiratory distress syndrome and acute lung injury bedside measurements of regional lung ventilation should be considered for optimizing ventilatory settings. The aim was to investigate the effect of positive end-expiratory pressure (PEEP) on regional ventilation in mechanically ventilated patients at the bedside by electrical impedance tomography. Eight mechanically ventilated patients were included in the study. PEEP levels were increased from 0 to 5, 10, 15 mbar and back to 0 mbar. Regional ventilation in 912 regions of the thorax was investigated at each PEEP by electrical impedance tomography. The obtained regions were divided in four groups: none (none and poorly ventilated regions including chest wall and mediastinum), bad, moderate and well-ventilated regions. Increasing the PEEP stepwise from 0 to 15 mbar decreased the non-ventilated regions (none: 540 regions at PEEP 0 and 406 regions at PEEP 15). In contrast, the other regions increased (bad: 316 regions at PEEP 0 and 380 regions at PEEP 15; moderate: 40 regions at PEEP 0 and 100 regions at PEEP 15; well: 0 region at PEEP 0 and 34 regions at PEEP 15 (median values)) indicating an improvement of regional ventilation. Increasing PEEP in mechanically ventilated patients reduces none ventilated regions (atelectasis). Furthermore, it leads to a shift from none and bad ventilated regions to moderately and well-ventilated regions. Electrical impedance tomography is a bedside technique and might be an alternative to computed tomography scan to assess aerated lung regions.


Broadband and robust adiabatic second-harmonic generation by a temperature gradient in birefringently phase-matched lithium triborate crystal.
Phase-matched nonlinear processes exhibit a tradeoff between the conversion efficiency and the acceptance bandwidth. Adiabatic nonlinear processes, in which the phase mismatch varies slowly along the interaction length, enable us to overcome this tradeoff, allowing an efficient frequency conversion with broad spectral and thermal bandwidths. Until now, the variation in the phase mismatch condition was mainly based on quasi-phase matching in ferroelectric crystals. However, this solution is limited to low power sources. Here, instead, we study the adiabatic second harmonic in birefringently phase-matched lithium triborate crystal, enabling us to handle much higher power levels. The variation in the phase mismatch is achieved by inducing a temperature gradient along the crystal. By using a 50 mm long crystal, the adiabatic process provided a temperature bandwidth of 18°C, 5.4 times wider than what is achieved when the same crystal is held at the fixed phase-matching temperature. The conversion efficiency exceeded 60% for a 0.9 millijoule pump pulse.


Identification and characterization of Src SH3 ligands from phage-displayed random peptide libraries.
We have used the Src homology 3 (SH3) domain to screen two phage-displayed random peptide libraries, each containing 2 x 10(8) unique members, and have identified a series of high affinity peptide ligands. The peptides possess similar proline-rich regions, which yield a consensus Src SH3-binding motif of RPLPPLP. We have confirmed this motif by screening a phage-displayed peptide library biased for SH3 ligands and identifying the same consensus sequence. Binding studies using synthetic peptides suggest that the RPLPPLP motif is important for SH3 binding and confers specificity for the Src SH3 domain, and that residues which flank the motif may also contribute to binding. Peptides that contain the RPLPPLP motif compete Src, but not Abl or phospholipase C gamma, SH3 interactions with SH3-binding proteins from cell lysates (IC50 = 1-5 microM). Furthermore, RPLPPLP-related peptides are able to accelerate progesterone-induced maturation of Xenopus laevis oocytes. A similar acceleration has been observed in oocytes treated with activated, but not normal, Xenopus Src, suggesting the possibility that the peptides are able to antagonize the negative regulation of Src activity by Src SH3 in vivo.


Surgical Outcomes by Early Airway Endoscopy Findings after Pediatric Staged Laryngotracheoplasty.
To determine how initial postoperative airway endoscopy findings after stent removal predict successful decannulation in children undergoing double-staged laryngotracheoplasty (dsLTP). Secondary objectives assessed timing of decannulation and number of endoscopic interventions needed after dsLTP. A case series with chart review included children who underwent dsLTP at a tertiary children's hospital between 2008 and 2021. Rates of decannulation, time to decannulation, and number of interventions after dsLTP were recorded for children with high- or low-grade stenosis at the first bronchoscopy after stent removal. Of the 65 children who were included, 88% had high-grade stenosis and 98% had a preoperative tracheostomy. Successful decannulation happened in 74% of the children, and 44% of the children were decannulated within 12 months of surgery. For children with low-grade stenosis at the first endoscopy after stent removal, 84% were successfully decannulated compared with 36% of the children with high-grade stenosis (p = 0.001). After dsLTP, children with high-grade stenosis required 7.5 interventions (SD: 3.3) compared with 4.0 interventions (SD: 3.0) for children with low-grade stenosis (p < 0.001). Decannulated children with high-grade stenosis necessitated more endoscopic procedures (7.0 vs. 3.7, p = 0.02). Time to decannulation was similar between children with high- and low-grade early postoperative stenosis (21.9 vs. 17.8 months, p = 0.63). Higher grade stenosis identified on the first airway endoscopy after suprastomal stent removal is correlated with lower decannulation rates and more postoperative endoscopic interventions. Although time to decannulation was not impacted by early stenosis grade, surgeons might utilize these early airway findings to counsel families and prognosticate possible surgical success. 4 Laryngoscope, 2023.


Characteristics and Workload of Pediatricians in China.
Although it is widely believed that China is facing a major shortage of pediatricians, the real situation of the current national status of pediatric human resources and their working conditions has not been evaluated to date. We administered a survey to 54 214 hospitals from all 31 provinces in mainland China from 2015 to 2016. Hospital directors of all secondary and tertiary hospitals with pediatric services and a random sample (10%) of primary hospitals provided information on number of pediatricians and their educational levels, specialties, workloads, dropout rates, and other hospital characteristics. A data set of medical resources and socioeconomic information regarding each region (1997-2016) was constructed from the Chinese National Statistics Bureau. The Gini coefficient was used to describe the geographical distributions of pediatricians and hospitals. There were 135 524 pediatricians in China or ∼4 pediatricians per 10 000 children. Pediatricians' average educational level was low, with ∼32% having only 3 years of junior college training after high school. The distribution of pediatricians was extremely skewed (Gini coefficient 0.61), and the imbalance of highly educated pediatricians was even more skewed (Gini coefficient 0.68). The dropout rate of pediatricians was 12.6%. Despite an increase in the Chinese government's financial investment in health over the last decade, physicians have been burdened with a greater workload. Uneven development of the pediatric care system, inadequately trained pediatricians, low job satisfaction, and unmet demand for pediatric care are the major challenges facing China's pediatric health care system.


Mechanisms of fibrosis in coal workers' pneumoconiosis. Increased production of platelet-derived growth factor, insulin-like growth factor type I, and transforming growth factor beta and relationship to disease severity.
To identify the clinical relevance of cytokines involved in the development of lung fibrosis observed in patients with coal workers' pneumoconiosis (CWP), we investigated the BAL fluid contents and AM secretions of three mediators that modulate fibroblast growth: platelet-derived growth factor (PDGF), Type I insulin-like growth factor (IGF-I), and transforming growth factor Type beta (TGF-beta). Our study population consisted of 25 patients with CWP (16 simple pneumoconiosis, SP, 9 progressive massive fibrosis, PMF, 9 control subjects, and 6 patients with idiopathic pulmonary fibrosis (IPF). The fibrotic potency of AM supernatants was also tested for their ability to promote the growth of a human lung fibroblast cell line appreciated by [3H]-thymidine incorporation. PDGF and IGF-I concentrations were increased in BAL fluids of patients with PMF compared with SP and control subjects, whereas TGF-beta concentration was significantly higher in BAL fluid of patients with SP compared with PMF and control subjects. PDGF, IGF-I, and TGF-beta concentrations in AM supernatants followed the same profile observed in BAL fluids, suggesting that AM is one of the main cell sources of PDGF, IGF-I, and TGF-beta in the lung of pneumoconiotic patients. After treatment by acidification, which activated the latent form of TGF-beta, AM from patients with SP induced an inhibition of [3H]-thymidine incorporation and fibroblast growth was restored after neutralization of TGF-beta by specific antibodies. In contrast, AM supernatants from patients with PMF and IPF promoted the proliferation of fibroblasts and treatment by acidification did not modify this effect.(ABSTRACT TRUNCATED AT 250 WORDS)


Review of laser speckle contrast techniques for visualizing tissue perfusion.
When a diffuse object is illuminated with coherent laser light, the backscattered light will form an interference pattern on the detector. This pattern of bright and dark areas is called a speckle pattern. When there is movement in the object, the speckle pattern will change over time. Laser speckle contrast techniques use this change in speckle pattern to visualize tissue perfusion. We present and review the contribution of laser speckle contrast techniques to the field of perfusion visualization and discuss the development of the techniques.


Tidal breathing parameters measured using structured light plethysmography in healthy children and those with asthma before and after bronchodilator.
Structured light plethysmography (SLP) is a light-based, noncontact technique that measures tidal breathing by monitoring displacements of the thoracoabdominal (TA) wall. We used SLP to measure tidal breathing parameters and their within-subject variability (v) in 30 children aged 7-16 years with asthma and abnormal spirometry (forced expiratory volume in 1 sec [FEV1] <80% predicted) during a routine clinic appointment. As part of standard care, the reversibility of airway obstruction was assessed by repeating spirometry after administration of an inhaled bronchodilator. In this study, SLP was performed before and after bronchodilator administration, and also once in 41 age-matched controls. In the asthma group, there was a significant increase in spirometry-assessed mean FEV1 after administration of bronchodilator. Of all measured tidal breathing parameters, the most informative was the inspiratory to expiratory TA displacement ratio (IE50SLP, calculated as TIF50SLP/TEF50SLP, where TIF50SLP is tidal inspiratory TA displacement rate at 50% of inspiratory displacement and TEF50SLP is tidal expiratory TA displacement rate at 50% of expiratory displacement). Median (m) IE50SLP and its variability (vIE50SLP) were both higher in children with asthma (prebronchodilator) compared with healthy children (mIE50SLP: 1.53 vs. 1.22, P < 0.001; vIE50SLP: 0.63 vs. 0.47, P < 0.001). After administration of bronchodilators to the asthma group, mIE50SLP decreased from 1.53 to 1.45 (P = 0.01) and vIE50SLP decreased from 0.63 to 0.60 (P = 0.04). SLP-measured tidal breathing parameters could differentiate between children with and without asthma and indicate a response to bronchodilator.


[Determination of genetic mutations in rpoB of the isolates of Mycobacterium tuberculosis complex those susceptibilities to rifampicin were interpreted as indeterminate by BrothMIC MTB].
The minimum inhibitory concentrations (MICs) to rifampicin (RFP) for Mycobacterium tuberculosis complex distribute bipartitely, the most susceptible, wild isolates showing < or = 0.03 microg/ml of MICs and the resistant isolates are >2.0 microg/ml. As the results, a very few number of isolates showing the MICs between 0.06 microg/ml to 2.0 microg/ml are still interpreted as "indeterminate" by BrothMIC MTB. In this communication, we determined genetic mutations in rpoB gene of the isolates of M. tuberculosis complex those MICs to RFP resulted in "indeterminate" interpretations. Through the direct base-sequencing, genetic mutation (s) in rpoB gene associated with amino acid substitution(s) were found in 21 of 27 clinical isolates of M. tuberculosis complex. All the isolates with 0.06 microg/ml of MICs were confirmed as being a wild type, whereas those with > or =0.125 microg/ml of MICs have a variety of genetic mutations. There found one exception, that is, a strain with 0.5 microg/ml of MIC revealed no mutation in rpoB gene. In addition to direct base-sequencing, a line probe assay, LiPA . Rif TB (Innogenetics N.V., Zwijnaarde, Belgium) was comparatively evaluated. The results obtained were highly correlated, LiPA . Rif TB giving comparable readings for 26 (96.3S) of 27 isolates tested. With these results, it can be concluded that the interpretive breakpoints for RFP MICs determined by BrothMIC MTB should be revised as follows: susceptible, < or =0.06 microg/ml, and resistant, > or =0.125 microg/ml. Secondly, LiPA . Rif TB gave an accurate and rapid interpretation for RFP resistance, but it may be concerned for the occasional false-susceptible readings.


A bioinformatics pipeline for high-throughput microbial multilocus sequence typing (MLST) analyses.
Multilocus sequence typing (MLST) analysis for semi-routine applications is hindered by the downstream, manually intensive steps of processing the raw sequence data files. This report describes the development of an MLST pipeline that automates DNA sequence editing and analysis in order to significantly reduce the time required for processing data. Validation using a pneumococcal dataset revealed complete agreement between the results generated by manual and automated workflows. The MLST pipeline was developed for both double-strand and single-strand sequencing.


[A case report of toxic shock syndrome after high orchiectomy].
We report our experience of toxic shock syndrome (TSS) in a 54-year-old male patient after high orchiectomy for testicular cancer. Four days after the surgery, he began to have diarrhea, high fever, and diffuse erythroderma followed by severe hypotension. There were no signs of postsurgical wound infection, so serious drug eruption was suspected. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the culture of the drain and result of skin biopsy, leading to the diagnosis of TSS. Following treatment with intravenous fluids, antibiotics, human immunoglobulin and corticosteroids, the symptoms went into remission. TSS progresses rapidly and becomes life-threatening if treatment is delayed. Therefore, when TSS is suspected in postsurgical patients who experience fever of 39 degrees C or higher, dermal erythema, shock, treatment should be started promptly.


The uvsY recombination protein of bacteriophage T4 forms hexamers in the presence and absence of single-stranded DNA.
A prerequisite to genetic recombination in the T4 bacteriophage is the formation of the presynaptic filament-a helical nucleoprotein filament containing stoichiometric amounts of the uvsX recombinase in complex with single-stranded DNA (ssDNA). Once formed, the filament is competent to catalyze homologous pairing and DNA strand exchange reactions. An important component in the formation of the presynaptic filament is the uvsY protein, which is required for optimal uvsX-ssDNA assembly in vitro, and essential for phage recombination in vivo. uvsY enhances uvsX activities by promoting filament formation and stabilizing filaments under conditions of low uvsX, high salt, and/or high gp32 (ssDNA-binding protein) concentrations. The molecular properties of uvsY include noncooperative binding to ssDNA and specific protein-protein interactions with both uvsX and gp32. Evidence suggests that all of these hetero-associations of the uvsY protein are important for presynaptic filament formation. However, there is currently no structural information available on the uvsY protein itself. In this study, we present the first characterization of the self-association of uvsY. Using hydrodynamic methods, we demonstrate that uvsY associates into a stable hexamer (s020,w = 6.0, M = 95 kDa) in solution and that this structure is competent to bind ssDNA. We further demonstrate that uvsY hexamers are capable of reversible association into higher aggregates in a manner dependent on both salt and protein concentration. The implications for presynaptic filament formation are discussed.


Practice points in utilizing local volunteers in community health projects.
Community volunteers are recruited for many health intervention projects. There are various motivations for the use of the volunteers and these include: the desire to reduce financial costs of projects/programmes; to encourage community ownership; ensure long-term sustainability of the health intervention; and to empower local communities through training offered the project. Health intervention measures working with community volunteers should not be implemented without due consideration of issues regarding mobilization and engagement, skills and motivation of the volunteers and their effectiveness and efficiency towards the attainment of the project goals. This paper discusses some tips that should be considered when community volunteers are used in resource-limited situations.


The gill maggot Salmincola salmoneus as an indicator of repeat spawning in Atlantic salmon Salmo salar.
The potential of the gill maggot Salmincola salmoneus for use as an indicator of repeat spawning in Atlantic salmon Salmo salar was studied in adult fish captured during their return migration to the River Alta (n = 659) and River Namsen (n = 540) in Norway. Eighty-eight and 49% of previous spawners identified by scale readings were infected with S. salmoneus in the two rivers, respectively. Salmincola salmoneus can be used as a reliable, rapid and objective field indicator of repeat spawning in S. salar as nearly all infected fish (99·4%) were identified as repeat spawners, although it is important to have appropriate background information on S. salmoneus prevalence on the postspawning individuals within the same population.


Unmet needs and health-related quality of life in young-onset dementia.
Young-onset dementia (YOD) causes specific challenges and issues that are likely to affect health-related quality of life (HRQOL). This study explored patient and caregiver HRQOL and its association with unmet needs in YOD. A cross-sectional design was used to study 215 community-dwelling YOD patients and their primary caregivers. Multiple linear regression analyses were performed to determine the relationship between unmet needs assessed with the Camberwell Assessment of Need for the Elderly scale and patient and caregiver HRQOL, controlling for other variables such as demographic characteristics, patient functional status, neuropsychiatric symptoms, and caregiver sense of competence. Patient HRQOL was not associated with unmet needs. However, we found that the unmet needs of both patient and caregiver were related to several domains of caregiver HRQOL. This study shows that patient and caregiver unmet needs are related to caregiver HRQOL in YOD. However, the relationship between HRQOL and unmet needs is complex. The assessment of unmet needs within the context of HRQOL seems to be an important prerequisite for personalizing care in YOD. Adjusting supportive services to match the individual needs and preferences of these young patients and their caregivers is likely to enhance their quality of life.


Development of a phase contrast imaging system based on a yttrium aluminum garnet laser with folded beam for observations of density fluctuations in compact helical system.
A near-infrared laser phase contrast optical system incorporating a folded beam was developed in order to measure the distribution of density fluctuations in a high-temperature plasma. The coherent light source used was an yttrium aluminum garnet laser stabilized by a ring oscillator. The probe beam system separates and reflects the incident and exiting beams with a polarizer and a fully reflective mirror with a waveplate. This system was employed with a compact helical system to detect fluctuations at the plasma edge.


Practical points in urinary proteomics.
During the proteomic era, one of the most rapidly growing areas in biomedical research is biomarker discovery, particularly using proteomic technologies. Urinary proteomics has become one of the most attractive subdisciplines in clinical proteomics, as the urine is an ideal source for the discovery of noninvasive biomarkers for human diseases. However, there are several barriers to the success of the field and urinary proteome analysis is not a simple task because the urine has low protein concentration, high levels of salts or other interfering compounds, and more importantly, high degree of variations (both intra-individual and inter-individual variabilities). This article provides step-by-step practical points to perform urinary proteome analysis, covering detailed information for study design, sample collection, sample storage, sample preparation, proteomic analysis, and data interpretation. The discussion herein should stimulate further discussion and refinement to develop guidelines and standardizations for urinary proteome study.


A 10-Food Group Dietary Diversity Score Outperforms a 7-Food Group Score in Characterizing Seasonal Variability and Micronutrient Adequacy in Rural Zambian Children.
Dietary diversity scores and dichotomous indicators derived from them are widely used to assess dietary quality, and specific scoring methods have been recommended for women and 6- to 23-mo-old children. However, there is no specific score recommended for older children and the effect of seasonal dietary changes on score performance is not well documented. We assessed performance of 2 recommended dietary diversity scores as indicators of dietary quality over 3 seasons. We conducted 7 repeat 24-h dietary recalls among 4- to 8-y-old rural Zambian children (n = 200) over 6 mo. Dietary diversity was assessed using a 7-food group score for assessing infant and young child feeding (DDS-IYCF) and a 10-food group score for use among women of reproductive age (DDS-W). Micronutrient intake adequacy was described by mean probability of adequacy (MPA) over 11 micronutrients. Longitudinal models were fit to test the association between each score and MPA overall and by season. Receiver operating characteristic (ROC) curves were used to describe indicator performance of each score. Mean ± SE scores were 4.11 ± 0.03 for DDS-IYCF and 4.39 ± 0.03 for DDS-W. Both scores varied by season, but DDS-W better reflected seasonal dietary changes. Across seasons, MPA increased 1-6 percentage points/unit increase in DDS-IYCF or 1-10 percentage points for DDS-W (P < 0.05). Score performance as a predictor of MPA > 0.75 was moderate, with area under the ROC curve values by season ranging from 0.63 to 0.77 for DDS-IYCF and from 0.66 to 0.72 for DDS-W. DDS-W performed better than DDS-IYCF in characterizing seasonal variability and micronutrient adequacy among rural Zambian children.


Induction of mucous cell metaplasia by tumor necrosis factor alpha in rat middle ear: the pathological basis for mucin hyperproduction in mucoid otitis media.
Mucoid otitis media (MOM), one of the leading causes of acquired hearing loss in children, is characterized by mucous cell hyperplasia in the middle ear cleft associated with mucin accumulation in the middle ear cavity. The factors that stimulate mucous cell metaplasia-hyperplasia and mucin hyperproduction are poorly understood. Recent studies demonstrated that tumor necrosis factor alpha (TNF-alpha), present in human middle ear effusion, stimulated mucin production in vitro and up-regulated mucin gene expression in vivo. These findings suggest that TNF-alpha is important in the development of mucous cell metaplasia-hyperplasia. This study demonstrated that inoculation of TNF-alpha into the middle ear cavity followed by eustachian tube obstruction stimulated mucous cell metaplasia-hyperplasia in the middle ear cleft, accompanied by abundant mucin or mucin-like glycoproteins in the middle ear effusion--a phenotype of MOM in humans. This finding suggests that TNF-alpha plays a key role in the pathogenesis of MOM through induction of mucous cell metaplasia-hyperplasia and mucin production.


Stereotactic MR-Guided Radiotherapy for Pancreatic Tumors: Dosimetric Benefit of Adaptation and First Clinical Results in a Prospective Registry Study.
Stereotactic MR-guided adaptive radiotherapy (SMART) is an attractive modality of radiotherapy for pancreatic tumors. The objectives of this prospective registry study were to report the dosimetric benefits of daily adaptation of SMART and the first clinical results in pancreatic tumors. All patients treated in our center with SMART for a pancreatic tumor were included. Patients were planned for five daily-adapted fractions on consecutive days. Endpoints were acute toxicities, late toxicities, impact of adaptive treatment on target volume coverage and organs at risk (OAR) sparing, local control (LC) rate, distant metastasis-free survival (DMFS), and overall survival (OS). Thirty consecutive patients were included between October 2019 and April 2021. The median dose prescription was 50 Gy. No patient presented grade > 2 acute toxicities. The most frequent grade 1-2 toxicities were asthenia (40%), abdominal pain (40%), and nausea (43%). Daily adaptation significantly improved planning target volume (PTV) and gross tumor volume (GTV) coverage and OAR sparing. With a median follow-up of 9.7 months, the median OS, 6-month OS, and 1-year OS were 14.1 months, 89% (95% CI: 70%-96%), and 75% (95% CI: 51%-88%), respectively, from SMART completion. LC at 6 months and 1 year was respectively 97% (95% CI: 79-99.5%) and 86% (95% CI: 61%-95%). There were no grade > 2 late toxicities. With a median follow-up of 10.64 months, locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC) patients (22 patients) had a median OS, 6-month OS, and 1-year OS from SMART completion of 14.1 months, 76% (95% CI: 51%-89%), and 70% (95% CI: 45%-85%), respectively. Nine patients underwent surgical resection (42.1% of patients with initial LAPC and 33.3% of patients with BRPC), with negative margins (R0). Resected patients had a significantly better OS as compared to unresected patients (p = 0.0219, hazard ratio (HR) = 5.78 (95% CI: 1.29-25.9)). SMART for pancreatic tumors is feasible without limiting toxicities. Daily adaptation demonstrated a benefit for tumor coverage and OAR sparing. The severity of observed acute and late toxicities was low. OS and LC rates were promising. SMART achieved a high secondary resection rate in LAPC patients. Surgery after SMART seemed to be feasible and might increase OS in these patients.


Cervical left pulmonary artery.
We detail what we believe to be the first reported case of a congenital 'Cervical Left Pulmonary Artery' in which an aberrant left pulmonary artery courses cranially into the mid-cervical neck before descending back into the thorax to the left pulmonary hilum. Due to the location and course of the artery, we believe that this anomaly is likely due to a developmental error of the sixth pharyngeal arch. Ultimately, the use of a reconstructed 3D computed tomography image provided detailed characterization of the unique anatomical variant, aiding in a successful surgical repair of the defect.


Selection of effective antisense oligodeoxynucleotides with a green fluorescent protein-based assay. Discovery of selective and potent inhibitors of glutathione S-transferase Mu expression.
Antisense oligodeoxynucleotides (AS-ODNs) are frequently used for the down-regulation of protein expression. Because the majority of potential antisense sequences lacks effectiveness, fast screening methods for the selection of effective AS-ODNs are needed. We describe a new cellular screening assay for the evaluation of the potency and specificity of new antisense sequences. Fusion constructs of the gene of interest and the gene encoding the enhanced green fluorescent protein (EGFP) are cotransfected with AS-ODNs to COS-7 cells. Subsequently, cells are analysed for expression of the EGFP fusion protein by flow cytometry. With the assay, we tested the effectiveness of a set of 15 phosphorothioate ODNs against rat glutathione S-transferase Mu1 (GSTM1) and/or Mu2 (GSTM2). We found several AS-ODNs that demonstrated potent, sequence-specific, and concentration-dependent inhibition of fusion protein expression. At 0.5 microm, AS-6 and AS-8 inhibited EGFP-GSTM1 expression by 95 +/- 4% and 81 +/- 6%, respectively. AS-5 and AS-10 were selective for GSTM2 (82 +/- 4% and 85 +/- 0.4% decrease, respectively). AS-2 and AS-3, targeted at homologous regions in GSTM1 and GSTM2, inhibited both isoforms (77-95% decrease). Other AS-ODNs were not effective or displayed non-target-specific inhibition of protein expression. The observed decrease in EGFP expression was accompanied by a decrease in GSTM enzyme activity. As isoform-selective, chemical inhibitors of GSTM and GSTM knock-out mice are presently unavailable, the selected AS-ODNs constitute important tools for the study of the role of GSTM in detoxification of xenobiotics and protection against chemical-induced carcinogenesis.


Distribution of oxidation specific lipid-protein adducts and apolipoprotein B in atherosclerotic lesions of varying severity from WHHL rabbits.
Antisera and monoclonal antibodies generated against autologous malondialdehyde-conjugated low density lipoprotein (MDA-LDL), 4-hydroxynonenal conjugated LDL (4-HNE-LDL), and the protein fragments of apoprotein B resulting from the copper oxidation of LDL, as well as antibodies against apoprotein B, were used to immunostain atherosclerotic lesions of varying severity from Watanabe heritable hyperlipemic rabbits. In macrophage-rich fatty streaks and transitional lesions, all of the antibodies recognizing oxidation specific epitopes exhibited predominantly cell-associated staining in particulate and annular patterns. This is in contrast to the limited, extracellular, diffuse staining obtained with the antibodies recognizing apoprotein B. In more advanced lesions containing areas with reduced numbers of cells, there was increased extracellular, diffuse staining with the antibodies against oxidation specific epitopes and co-localization with apoprotein B. In addition, there were annular staining patterns associated with the necrotic core and increased staining of intimal and medial smooth muscle cells. We interpret these data as suggesting that in areas of lesions rich in macrophages, LDL is oxidized and taken up by the cells. In more advanced lesions that are relatively devoid of macrophages, both native and oxidized LDL, as well as oxidation products released from dead and decaying cells, are trapped in the matrix, out of reach of those cells capable of accumulating oxidized LDL.


Evaluation of serological and molecular tests used to identify Toxoplasma gondii infection in pregnant women attended in a public health service in São Paulo state, Brazil.
Toxoplasmosis during pregnancy can have severe consequences. The use of sensitive and specific serological and molecular methods is extremely important for the correct diagnosis of the disease. We compared the ELISA and ELFA serological methods, conventional PCR (cPCR), Nested PCR and quantitative PCR (qPCR) in the diagnosis of Toxoplasma gondii infection in pregnant women without clinical suspicion of toxoplasmosis (G1=94) and with clinical suspicion of toxoplasmosis (G2=53). The results were compared using the Kappa index, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. The results of the serological methods showed concordance between the ELISA and ELFA methods even though ELFA identified more positive cases than ELISA. Molecular methods were discrepant with cPCR using B22/23 primers having greater sensitivity and lower specificity compared to the other molecular methods.


A novel two-dimensional MgB6 crystal: metal-layer stabilized boron kagome lattice.
Based on first-principles calculations, we designed for the first time a boron-kagome-based two-dimensional MgB6 crystal, in which two boron kagome layers sandwich a triangular magnesium layer. The two-dimensional lattice is metallic with several bands across the Fermi level, and among them a Dirac point appears at the K point of the first Brillouin zone. This metal-stabilized boron kagome system displays electron-phonon coupling, with a superconductivity critical transition temperature of 4.7 K, and thus it is another possible superconducting Mg-B compound besides MgB2. Furthermore, the proposed 2D MgB6 can also be used for hydrogen storage after decoration with Ca. Up to five H2 molecules can be attracted by one Ca with an average binding energy of 0.225 eV. The unique properties of 2D MgB6 will spur broad interest in nanoscience and technology.


Doxorubicin induces de novo expression of N-terminal-truncated matrix metalloproteinase-2 in cardiac myocytes.
Anthracyclines, such as doxorubicin, are commonly prescribed antineoplastic agents that cause irreversible cardiac injury. Doxorubicin cardiotoxicity is initiated by increased oxidative stress in cardiomyocytes. Oxidative stress enhances intracellular matrix metalloproteinase-2 (MMP-2) by direct activation of its full-length isoform and (or) de novo expression of an N-terminal-truncated isoform (NTT-MMP-2). As MMP-2 is localized to the sarcomere, we tested whether doxorubicin activates intracellular MMP-2 in neonatal rat ventricular myocytes (NRVM) and whether it thereby proteolyzes two of its identified sarcomeric targets, α-actinin and troponin I. Doxorubicin increased oxidative stress within 12 h as indicated by reduced aconitase activity. This was associated with a twofold increase in MMP-2 protein levels and threefold higher gelatinolytic activity. MMP inhibitors ARP-100 or ONO-4817 (1 μM) prevented doxorubicin-induced MMP-2 activation. Doxorubicin also increased the levels and activity of MMP-2 secreted into the conditioned media. Doxorubicin upregulated the mRNA expression of both full-length MMP-2 and NTT-MMP-2. α-Actinin levels remained unchanged, whereas doxorubicin downregulated troponin I in an MMP-independent manner. Doxorubicin induces oxidative stress and stimulates a robust increase in MMP-2 expression and activity in NRVM, including NTT-MMP-2. The sarcomeric proteins α-actinin and troponin I are, however, not targeted by MMP-2 under these conditions.


Paratesticular malignant peripheral nerve sheath tumour: a case report.
Primary malignant peripheral nerve sheath tumours (MPNST) of intrascrotal extra testicular site are extremely rare with only few cases reported in literature. These are highly malignant tumours most often associated with neurofibromatosis. The incidence in general population is 0.001%. A 35-year-old male presented with swelling of the scrotal sac of three months duration. There were no features of neurofibromatosis. The lesion was excised and was diagnosed as MPNST. The patient developed recurrence within two months.


Influence of diet, cortisol and insulin on the activity of pyruvate carboxylase and phosphoenolpyruvate carboxykinase in the rat liver.
The influence of nutritional factors, such as fasting (24, 48 and 72 hours), protein free and high protein diets, and endocrine factors (cortisol and insulin) on the activity of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC) in adult rats was studied. The circadian rhythm in the activity of these enzymes was studied at two protein levels: 15% and 50%. Under all conditions which favored gluconeogenesis the activity of PEPCK increased. Cortisol did not further increase the activity of PEPCK in rats fed a high protein diet. Regardless of the protein content of the diet, insulin did not reduce PEPCK activity. Dietary protein level had no influence on the usual rhythm of activity of PEPCK. On the other hand, the high protein diet increased it threefold. Under all experimental conditions we observed no changes in PC activity. This is probably due to the fact that PC is a constitutive enzyme and therefore is not adaptative.