Bone mineral density, bone turnover markers and cytokines in alcohol-induced cirrhosis.
Liver cirrhosis is a risk factor for osteoporosis. However, the pathogenesis of the bone mass loss in patients with alcohol-induced cirrhosis (AC) is not well understood. Serum concentrations of soluble tumour necrosis factor receptor (sTNF-R55), neopterin and soluble interleukin 2 receptor (sIL-2R), activation markers of cellular immunity, correlate with clinical activity and severity of the AC. The aim of this study is to evaluate the association of these soluble markers with the development of osteoporosis in patients with AC. We studied 33 consecutive patients with AC and 24 healthy volunteers. Bone mineral density (BMD) was measured by X-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). Neopterin was measured by radioimmunoassay. Serum concentrations of sTNF-R55 and sIL-2R were measured by enzyme immunoassay. We also determined serum levels of osteocalcin and bone alkaline phosphatase as biochemical markers of bone formation, and deoxypyridinoline urinary excretion (D-Pyr) as marker of bone resorption. Patients with AC had reduced BMD (expressed as z-score) in all sites (LS: P < 0.001 and FN: P < 0.05). Serum concentrations of sTNF-R55 were significantly higher in patients with both AC and osteoporosis than in those with only AC (P < 0.001). Serum levels of sTNF-R55 positively correlated with D-Pyr urinary excretion (r = 0.354; P = 0.01). Serum levels of sIL-2R were significantly higher in patients with both AC and osteoporosis than in those with only AC (P < 0.05). There is a relation between activation of the cellular immunity and osteoporosis in AC. Bone mass loss could be related to the increased bone resorption found in these patients.


Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets.
Polyamines are essential for cell growth and beneficial for intestinal maturation. To evaluate the effects of putrescine on alleviating intestinal atrophy and underlying molecular mechanisms, both in vivo feeding trial and in vitro cell culture were conducted. Weanling pigs were fed a diet supplemented with 0, 0.1%, 0.2% or 0.3% putrescine dihydrochloride, whereas porcine intestinal epithelial cells (IPEC-J2) were challenged with lipopolysaccharide (LPS) in the presence of 200 μmol/L putrescine. Dietary supplementation with 0.2% putrescine dihydrochloride decreased the incidence of diarrhea with an improvement in intestinal integrity. Inhibition of ornithine decarboxylase activity decreased the proliferation and migration of IPEC-J2 cells, and this effect was alleviated by the supplementation with putrescine. The phosphorylation of extracellular signal regulated kinase and focal adhesion kinase was enhanced by putrescine. LPS increased the expression of inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-8], and inhibited cell proliferation and migration in IPEC-J2 cells. Adding exogenous putrescine suppressed the expression of TNF-α, IL-6 and IL-8, and recovered cell migration and proliferation in LPS-treated IPEC-J2 cells. Dietary putrescine supplementation also reduced the mRNA levels of TNF-α, IL-6 and IL-8 and their upstream regulator nuclear receptor kappa B p65 subunit in the jejunal mucosa of piglets. Dietary supplementation with putrescine mitigated mucosal atrophy in weanling piglets through improving anti-inflammatory function and suppressing inflammatory response. Our results have important implications for nutritional management of intestinal integrity and health in weanling piglets and other neonates.


Comparative study of five beta-adrenoceptor blocking agents on sinoatrial conduction time in isolated blood-perfused canine atria.
We studied the effects of five beta-adrenoceptor blocking agents (propranolol, atenolol, sotalol, oxprenolol and carteolol) on sinus cycle length (SCL), sinoatrial conduction time (SACT) measured with a constant atrial pacing technique, and atrial developed tension (DT), using isolated blood-perfused canine atria. Except for carteolol, all tested beta-blockers were infused into the sinus node artery at a rate of 1-4 micrograms/min, and carteolol was given continuously at a rate of 0.1-0.4 micrograms/min. Atenolol and sotalol as well as propranolol prolonged SCL and SACT and reduced DT dose-dependently, although propranolol had more potent negative chrono-, dromo- and inotropisms than atenolol and sotalol. Oxprenolol did not change SCL significantly, but lengthened SACT at higher doses and decreased DT in a dose-related manner. Carteolol did not cause any significant changes in the three parameters. The relative potencies on deceleration of SA conduction on the basis of administration of doses which seems to be equipotent as to beta-blocking effect are as follows: propranolol greater than atenolol = sotalol greater than oxprenolol = carteolol. These results suggest that the membrane stabilizing action of beta-blockers may lengthen SACT but that the intrinsic sympathomimetic action of beta-blockers may resist such a prolongation of SACT.


EE-ACML: Energy-Efficient Adiabatic CMOS/MTJ Logic for CPA-Resistant IoT Devices.
Internet of Things (IoT) devices have strict energy constraints as they often operate on a battery supply. The cryptographic operations within IoT devices consume substantial energy and are vulnerable to a class of hardware attacks known as side-channel attacks. To reduce the energy consumption and defend against side-channel attacks, we propose combining adiabatic logic and Magnetic Tunnel Junctions to form our novel Energy Efficient-Adiabatic CMOS/MTJ Logic (EE-ACML). EE-ACML is shown to be both low energy and secure when compared to existing CMOS/MTJ architectures. EE-ACML reduces dynamic energy consumption with adiabatic logic, while MTJs reduce the leakage power of a circuit. To show practical functionality and energy savings, we designed one round of PRESENT-80 with the proposed EE-ACML integrated with an adiabatic clock generator. The proposed EE-ACML-based PRESENT-80 showed energy savings of 67.24% at 25 MHz and 86.5% at 100 MHz when compared with a previously proposed CMOS/MTJ circuit. Furthermore, we performed a CPA attack on our proposed design, and the key was kept secret.


Evolutionary evidence on suitability of SecD as a target for development of antibacterial agents against Staphylococcus aureus.
Staphylococcus aureus causes many infections and its drug resistance is a worrying challenge for medical care. The SecD subunit of Sec secretion system in methicillin-resistant S. aureus is an attractive target because SecD dysfunction leads to the death of bacteria and SecD as a target is more efficient than SecA and SecF. Evolution could have made SecD to become insensitive to antibacterial agents although the drugs directly against SecD have yet to develop. So far, no detailed information on SecD evolution has been available, thus 2686 SecD sequences with full taxonomic information from kingdom to species were analyzed. First, the variance of pairwise p-distance was evaluated for each taxonomic group. Second, the variance was further partitioned into intergroup and intragroup variances for quantification of horizontal and vertical gene transfer. Third, phylogenetic tree was built to trace the evolutionary pathway. The results showed that overall evolution of SecDs appears to have undergone horizontal and vertical gene transfer. Only 0.5% horizontal transfers were found between any two SecDs in S. aureus, 6.8% and 8.8% horizontal transfers were found between any two Staphylococcus SecDs from different and the same species, and only one SecD from S. aureus was located far away from its sister cluster. Thus, statistic and evolutionary analyses demonstrate that the SecDs from staphylococcus species have a small chance of mutating, and provide taxonomic evidence to use the SecD as a potential target for new generation of antibacterial agents against S. aureus.


Investigation into the in vivo mechanism of diosmetin in patients with breast cancer and COVID-19 using bioinformatics.
Patients with breast cancer are prone to SARS-CoV-2 infection [the causative virus of coronavirus disease (COVID-19)] due to their lack of immunity. In the current study, we examined the mechanism of action of Diosmetin, a flavonoid with anti-inflammatory properties, in patients with BRCA infected with SARS-CoV-2.We used bioinformatics technology to analyze the binding ability, biological function, and other biological characteristics of Diosmetin in vivo and examine the core target and potential mechanism of action of Diosmetin in patients with patients with breast cancer infected with SARS-CoV-2. A prognostic model of SARS-COV-2-infected breast cancer patients was constructed, and the core genes were screened out, revealing the correlation between these core genes and clinicopathological characteristics, survival rate, and high-risk and low-risk populations. The docking results revealed that Diosmetin binds well to the core genes of patients with breast cancer with COVID-19. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that Diosmetin inhibited inflammation, enhanced immune function, and regulated the cellular microenvironment in patients with BRCA/COVID-19. For the first time, we reveal the molecular functions and potential targets of Diosmetin in patients with breast cancer infected with SARS-CoV-2, improving the reliability of the new drug and laying the foundation for further research and development.


Meta-Analysis on Parent-Teacher Agreement on Preschoolers' Emotional and Behavioural Problems.
Based on a meta-analysis, this study aimed to examine cross-informant agreement between parents and teachers about Internalizing, Externalizing and Total Problems in preschool children using community and clinical samples and to test the effects of the type of sample, the measure used for assessments, and child sex on agreement between informants. The meta-analysis involved 23 studies assessing cross-informant agreement for preschool children. Informants were parents and teachers. The level of cross-informant agreement tended to be low. Meta-regression analyses showed that the child's sex, the type of sample, and the measure used for assessments did not predict the level of cross-informant agreement on emotional and behavioural problems. The findings were in line with previous research results. Furthermore, the studied variables did not contribute to the prediction of agreement, suggesting the development of further studies that focus on other variables that may interfere with agreement in informants' reports and will contribute to explaining different ratings of internalizing and externalizing problems in preschool-aged children.


Role of the prodomain in folding and secretion of rat pancreatic carboxypeptidase A1.
Pancreatic carboxypeptidase A1 (CPA1) is synthesized as an inactive precursor, proCPA1, which is processed to the active enzyme by the proteolytic removal of the 95-amino acid N-terminal prodomain. Purified rat proCPA1 is renatured in vitro after denaturation in guanidine or in guanidine plus reducing agents. In contrast, purified CPA1 is not renatured under any of the conditions tested. While proCPA1 is secreted in yeast when fused to the alpha-factor signal sequence in place of its endogenous signal sequence, mature CPA1 is not secreted and is trapped and degraded intracellularly. Thus, in addition to maintaining CPA1 in the inactive state, the prodomain promotes folding and secretion of the proenzyme. Neither of these functions can be restored by supplying the prodomain to CPA1 in trans. The three-dimensional structure of porcine proCPA reveals a number of extensive contacts made between the prodomain and the enzyme active site which account for its inhibitory properties [Guasch et al. (1992) J. Mol. Biol. 224, 141-157]. Among these contacts are salt bridges formed between Arg-71 and Asp-A36 and between Arg-124 and Asp-A89. Mutation of any of these four residues inhibits secretion of proCPA1 from yeast and results in its intracellular degradation. The effect of the mutations on secretion suggests that interactions which stabilize the binding of prodomain to the native enzyme active site may also be important for the successful folding of proCPA1.


Relationships Between Depressive Symptoms, Anxiety, Impulsivity and Cigarette and E-cigarette Use Among Young Adults.
Depression and anxiety have been associated with cigarette use among young people. Higher impulsivity has also been associated with increased smoking behavior. However, relatively less is known about the associations between depression, anxiety, impulsivity and e-cigarette use and how these associations compare with the associations between depression, anxiety, impulsivity and cigarette smoking. In addition, little is known about how impulsivity influences the relationships between depression, anxiety, cigarette, and e-cigarette use. This study tested the hypothesis that higher depression and anxiety symptoms are associated with higher e-cigarette use and cigarette smoking in a similar way, and that these associations would be stronger among those with higher impulsivity. A sample of 2,622 young adults (18-25 year olds; 54% women) enrolled in 4-year and 2-year colleges in Hawai'i participated in a cross-sectional survey. Approximately 68% of the sample reported no use of either e-cigarettes or cigarettes, 13% reported only e-cigarette use, 9% reported only cigarette smoking, and 11% reported use of both. The study found that higher depressive and anxiety symptoms and higher impulsivity were significantly associated with current cigarette and e-cigarette use. For example, one unit increases in depression, anxiety, and impulsivity were associated with 34%, 17%, and 38% increased odds of e-cigarette use versus non-use, respectively. Impulsivity was found to significantly moderate the association between higher anxiety and higher cigarette smoking, such that the association was stronger among those with higher impulsivity. Impulsivity was not found to moderate any other association. Results suggest that tobacco product use prevention education should target children and young adults with higher internalizing symptoms, with particular attention to those who show higher impulsivity.


[Clinical effect of alanyl glutamine in the treatment of patients with gastrointestinal function obstacle caused by severe phorate poisoning].
Objective: To observe the therapeutic efficacy of alanyl glutamine injection on patients with gastrointestinal function obstacle caused by severe phorate poisoning. Methods: A total of 80 eligible patients with gastrointestinal function obstacle caused by severe phorate poisoning were randomly divided into the control group (n=40) and treatment group (n=40) . The control group was treated with the conventional therapy, which included forbidden diet, atropine, pralidoxime iodide, anti-inflammatory, albumin infusion, ω-3 fish oil fat emulsion, protection of organs function, blood perfusion, and Fat Emulsion, Amino Acids (17) and Glucose Injection. The treatment group was treated with alanyl glutamine injection plus the conventional therapy. To observe the time of recovering to normal of gastrointestinal function between the two groups, compared the AChE activity and changes of prealbumin, albumin and total protein of the two groups respectively. Furthermore, the total atropine dosage, the total pralidoxime iodide dosage and ICU stay time between the two groups were also compared. Results: The gastrointestinal function recovery time of patients in the treatment group was less than the control group, the difference was statistically significant (P<0.05) . From the third day of treatment, the serum cholinesterase activity of the treatment group was higher than the control group, the difference was statistically significant (P<0.05) . On the 5th day and 10th day of the treatment, the prealbumin, albumin and total protein of the treatment group were significantly higher than these indexes of the control group in the same period, the difference were statistically significant (P<0.05) . The total atropine dosage, the total pralidoxime iodide dosage and ICU stay time in the treatment group were lower than the control group, the difference were statistically significant (P<0.05) . Conclusion: Alanyl glutamine injection has a great therapeutic effect for gastrointestinal function obstacle patients caused by severe phorate poisoning.


Internalization and trafficking of the human and rat growth hormone-releasing hormone receptor.
Internalization and intracellular trafficking of the growth hormone-releasing hormone receptor (GHRH-R) were studied in rat anterior pituitary and human (h) and rat (r) GHRH-R-transfected BHK cells, with the GHRH agonist, [N(alpha)-5-carboxyfluoresceinyl-D-Ala(2), Ala(8), Ala(15), Lys(22)]hGHRH(1-29)NH(2) (Fluo-GHRH). Time- and temperature-dependent internalization of stimulated GHRH-R was blocked by phenyl arsine oxide (PAO) in both cell types. In anterior pituitary and rGHRH-R-transfected BHK cells, only filipin III and cerulenin blocked receptor-mediated internalization of Fluo-GHRH while in hGHRH-R-transfected BHK cells, only hyperosmolar sucrose inhibited this process. These results suggest that hGHRH-R internalization is clathrin-dependent, while fatty acid acylation of rGHRH-R appears to be a prerequisite to caveolin-dependent internalization. Experiments in anterior pituitary using Bodipy-FL-C(5) ganglioside GM1, a specific marker of lipid rafts such as caveolae, confirmed this latter pathway. Co-localization of Fluo-GHRH with LysoTracker indicated that Fluo-GHRH was directed to acidic organelles in both cell types. Finally, studies using cycloheximide and monensin showed that upon stimulation with GHRH, an optimal concentration of functional GHRH-R was maintained at the plasma membrane due to de novo synthesis and recycling in pituitary cells and to de novo synthesis solely in hGHRH-R-transfected BHK cells. This first study on the dynamics of the GHRH/GHRH-R complexes using fluorescence imaging in a native environment compared to cell system models, revealed that both receptor primary structure and concentration at the plasma membrane play important roles in internalization and trafficking of specific G-protein-coupled receptors (GPCR).


Monophosphoryl lipid A induces pharmacologic 'preconditioning' in rabbit hearts without concomitant expression of 70-kDa heat shock protein.
The purpose of this study was to evaluate the protective effect of a new endotoxin analogue, monophosphoryl lipid A (MLA) in a rabbit model of myocardial ischemia/reperfusion and to show if this protection was mediated via synthesis of 70 kDa heat shock protein (HSP 70). Three groups of New Zealand White rabbits underwent 30 min coronary occlusion, followed by 4 hours reperfusion. First group of rabbits (n = 6) were treated with 0.35 ml vehicle (40% propylene glycol, 10% ethanol in water). The second and third group of rabbits (n = 6-8) were treated with MLA (35 micrograms/kg, i.v.) 12 and 24 hours prior to ischemia and reperfusion. MLA treatment either 12 or 24 h prior to ischemia/reperfusion demonstrated significantly reduced infarct size (12.5 +/- 1.7 and 14.7 +/- 2.1% for 12 and 24 h) when compared with vehicle control (40.4 +/- 8.6%, mean +/- S.E.M, p < 0.05). No significant differences in the infarct size was observed between the 12 and 24 h MLA treated groups. The area at risk was not significantly different between the three groups. Baseline values of heart rate, systolic and diastolic blood pressure were not significantly different between the control and MLA treated groups. However, the systolic as well as diastolic blood pressure during reperfusion were significantly lower in rabbits treated with MLA. Western blot analysis of the protein extracts of the hearts (n = 2/group) demonstrated no increase in the expression of the inducible form of HSP 70 following treatment with MLA. We conclude that MLA has significant anti-infarct effect in rabbit which is not mediated by the cardioprotective protein HSP 70. The anti-infarct effect of this drug is superior to the reported protective effects of delayed ischemic or heat stress preconditioning. We hypothesize that the pharmacologic preconditioning afforded by MLA is accomplished via a unique pathway that bypasses the usual intracellular signaling pathways which lead to the myocardial protection with the expression of heat shock proteins.


Correlation of two bioluminescence and one fluorogenic bioassay for the detection of toxic chemicals.
The linear correlation between the EC50 values of 50 substances obtained in luminescence bioassays using Vibrio fischeri and Vibrio harveyi and in a fluorogenic bioassay using Escherichia coli was investigated. As a result, a significant correlation was found between the said values in all three toxicity tests. The bioassay using V. harveyi had a sensitivity similar to that of the fluorogenic bioassay, and the bioassay using V. fischeri was the least sensitive of all. The sensitivity of the three bioassays for each of the tested substances, chiefly heavy metals, organic solvents, orgnochlorated compounds, and pesticides, differed in the majority of the cases. The three bioassays were quantified using the same laboratory apparatus and the data were processed in the same way. The possibility of designing a battery of toxicity tests that can be performed using the same apparatus but different organisms and parameters is discussed.


MicroRNA-206: Effective Inhibition of Gastric Cancer Progression through the c-Met Pathway.
MicroRNAs are endogenous short chain nucleotide RNAs that regulate gene function by direct binding of target mRNAs. In this study, we investigated the effects of microRNA-206 (miR-206) on the development of gastric cancer. miR-206 was first confirmed to be downregulated in gastric cancer specimens. Conversely, upregulation of c-Met was confirmed in tissue samples of human gastric cancer, with its level inversely correlated with miR-206 expression. Introduction of miR-206 inhibited cellular proliferation by inducing G1 cell cycle arrest, as well as migration and invasion. Moreover, important proliferation and/or migration related molecules such as c-Met, CDK4, p-Rb, p-Akt and p-ERK were confirmed to be downregulated by Western blot analysis. Targeting of c-Met also directly affected AGS cell proliferation, migration and invasion. In vivo, miR-206 expressing tumor cells also displayed growth delay in comparison to unaffected tumor cells. Our results demonstrated that miR-206 suppressed c-Met expression in gastric cancer and could function as a potent tumor suppressor in c-Met overexpressing tumors. Inhibition of miR-206 function could contribute to aberrant cell proliferation and migration, leading to gastric cancer development.


Doppler measurements of maternal and fetal blood flow.
Data accumulated over the last decade suggest that Doppler flow velocity waveforms can be used to study both maternal and fetal circulation. Information obtained with this technique appears useful as a screen for both maternal and fetal risk, as an aid to understanding perinatal anatomy and physiology, and as an adjunct to standard means of fetal surveillance.


Intercalation of Nanosized Fe3C in Iron/Carbon To Construct Multifunctional Interface with Reduction, Catalysis, Corrosion Resistance, and Immobilization Capabilities.
As a robust reducing system in industrial wastewater treatment, iron/carbon (Fe/C) microelectrolysis suffers from surface passivation and low utilization efficiency. Herein, we introduced Fe3C into the Fe/C system to develop a core-shell Fe0/Fe3C/C nanorod with a multifunctional interface (Fe3C/C) providing reduction, catalysis, adsorption, and corrosion resistance. The results proved that the fabricated Fe0/Fe3C/C possesses 5.6 times higher reduction capacity (220 mg/g) for Cr(VI) reduction but a relatively lower Fe leakage (2.7 mg/L) than Fe/C. On the basis of the results of electrochemical characterization (Tafel polarization curves and electrochemical impedance spectroscopy), the corrosion-resistant Fe3C/C shell can significantly prevent surface passivation of the Fe0 core, whereas Fe3C efficiently catalyzes electron transfer from the inner Fe0 to the external carbon surface. Moreover, the reductive species involved in Cr(VI) removal were identified as hydrogen atoms, adsorbed Fe(II) ions, and electrons tunneling from Fe0. STEM, XPS, and Mössbauer spectroscopies were further adopted to characterize the interface reaction of Fe0/Fe3C/C during the Cr(VI) removal process. Finally, the reaction mechanism for Cr(VI) reduction over Fe0/Fe3C/C was proposed, and the distribution of active sites was inferred.


Incomplete total body protein recovery in adolescent patients with anorexia nervosa.
Bone health and growth during adolescence require adequate total body protein (TBPr). Renutrition for patients with anorexia nervosa (AN) should aim to normalize body composition and to recover both fat mass and TBPr. We intended to analyze predictors of protein status, including exercise status, in adolescents with AN and to investigate whether weight gain would replenish body protein deficits. We assessed TBPr in a longitudinal, observational study as height-adjusted nitrogen index (NI) using in vivo neutron activation analysis in 103 adolescents with AN [mean ± SD age, 15.6 ± 1.4 y; body mass index (BMI, in kg/m2), 16.5 ± 1.6] at the commencement of inpatient refeeding (T0), in 56 of these patients 7 mo thereafter as outpatients (T1), and in age-matched controls (C; n = 51, 15.5 ± 2.1 y, BMI 20.7 ± 1.9). Lean tissue and fat mass were assessed by dual-energy X-ray absorptiometry. BMI, BMI standard deviation score, and lean tissue mass were tested as predictors of protein status using receiver operating characteristic analysis. At T0, NI was decreased in AN (AN, 0.88 ± 0.10 compared with C, 1.00 ± 0.08, P < 0.001). In 34%, the patients showed protein depletion. Patients classified as ``exercisers'' had a higher NI than did ``nonexercisers'' (0.89 ± 0.11 compared with 0.85 ± 0.08, P = 0.045). BMI, BMI standard deviation score, and lean tissue mass did not show potential as predictors of protein status. Despite increases in weight (+6.9 ± 4.5 kg), and BMI (+2.5 ± 1.7), protein status did not improve (TBPr T0, 8.0 ± 1.1 kg; T1, 8.1 ± 1.0 kg, P = 0.495). In an AN subgroup at 7 mo matched with controls in age (AN, 16.5 ± 1.1 y; C, 16.2 ± 1.8 y) and BMI (AN, 20.5 ± 1.4; C, 20.7 ± 1.3), protein status was still not normalized in AN (NI: AN, 0.89 ± 0.09 compared with C, 1.00 ± 0.07, P < 0.001). Adolescents recovering from AN remained protein depleted at 7 mo after baseline assessment, even though they were weight restored.


Transcriptional and Post-Transcriptional Regulation of RNA Levels in Maize Mitochondria.
Relatively little is known about the mechanisms that govern the expression of plant mitochondrial genomes. We have addressed this problem by analyzing the transcriptional activity of different regions of the maize mitochondrial genome using both in vivo and isolated mitochondrial pulse-labeling systems. The regions examined included the protein genes atpA, atp6, and coxII, the 26S, 18S, and 5S rRNA genes, and sequences surrounding the rRNA genes. The rRNAs were found to be transcribed at rates fivefold to 10-fold higher than the protein genes. These rate differences are comparable with the differences in abundance of these species in the total or steady-state RNA population. Pulse-labeled RNA unexpectedly detected transcription of all regions examined, including approximately 21 kilobases of presumed noncoding sequences flanking the rRNA genes for which stable transcripts were not detected. The results obtained with RNA labeled for short pulses in vivo and in isolated mitochondria were similar, suggesting that isolated mitochondria provide a faithful run-on transcription assay. Our results indicate that the absence in total RNA of transcripts homologous to a given region of maize mitochondrial DNA does not necessarily exclude transcriptional activity of that region and that both transcriptional and post-transcriptional processes play important roles in maize mitochondrial genome expression.


Chinese Livery Drivers' Perspectives on Adapting a Community Health Worker Intervention to Facilitate Lung Cancer Screening.
Chinese immigrant livery drivers with a smoking history are at high risk for lung cancer. A culturally adapted community health worker (CHW) program may be an effective approach to increase lung cancer screening (LCS) uptake in this underserved group. Five focus groups were conducted with 39 Chinese immigrant male livery drivers with a smoking history in New York City to assess their needs, priorities, and preferences regarding the proposed intervention. Transcripts were qualitatively analyzed using Atlas. ti. Focus group participants were uncertain about whether smoking was associated with cancer, unfamiliar with LCS, and reported numerous barriers to LCS uptake. Most believed a CHW program to facilitate LCS would be acceptable and feasible, if tailored to meet their needs. Our results have implications for improving access to early detection of lung cancer and preventive care (e.g., culturally appropriate smoking cessation and health education programs) for Chinese livery drivers.


Fabrication of gap-optimized CMUT.
A recently introduced set up of capacitive micromachined ultrasonic transducers (cMUT) combines a conductive membrane above a structured sacrificial layer. All previous approaches either require an additional metallic electrode or do not possess a structured sacrificial layer and, consequently, may make exact adjustment of the membrane dimensions difficult. The present set ups are especially suited for the fabrication of cMUT with gap heights ranging between 50 nm and 2 microm between the electrodes. Large gaps are a prerequisite to enabling sufficient deflections of the membrane and, therewith, to generating high pressure gradients. On the other hand, small gap sizes are desirable for detecting weak ultrasonic sources. This paper focuses on the fabrication process of cMUT to realize electrode separation above 500 nm and, in addition, on the manufacturing of cMUT with gaps below 500 nm. The successful realization has been proven by some basic experimental investigations. Finally, the fundamental equations of a frequently chosen simulation model are documented, as a number of ambiguities exist in the common literature.


Soliton breathing induced by stimulated Raman scattering and self-steepening in octave-spanning Kerr frequency comb generation.
We investigate the impact of stimulated Raman scattering (SRS) and self-steepening (SS) on breather soliton dynamics in octave-spanning Kerr frequency comb generation. SRS and SS can transform chaotic fluctuations in cavity solitons into periodic breathing. Furthermore, with SRS and SS considered, bandwidth of the soliton breathes more than two times stronger. The simultaneous presence of SRS and SS also make the soliton breathe slower and degrades the coherence of the soliton.


Modelling preeclampsia: a comparative analysis of the common human trophoblast cell lines.
Preeclampsia remains a challenge without an effective therapy. Evidence supports targetability of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), which are released excessively from the placenta under ischemic and hypoxic stresses. We compared four trophoblast cell lines, BeWo, Jar, Jeg-3, and HTR-8/SVneo, in order to identify a suitable model for drug screening. Cultured trophoblasts were exposed to 1% oxygen vs. normoxia for 24-48 hr; human umbilical vein and aortic endothelial cells were included for comparison. Supernatant sFlt-1 and sEng concentrations were measured by ELISA, and sFlt-1 mRNA expression determined by RT-PCR. Cellular responses to experimental therapeutics were explored. All four trophoblast lines secreted sEng, which did not increase by hypoxia. BeWo, Jar, and Jeg-3 exhibited significantly enhanced expression of sFlt-1 i13 and e15a mRNA in response to hypoxia; however, only BeWo released a detectable level of sFlt-1 protein, which was doubled by hypoxia. In contrast, hypoxia decreased sFlt-1 mRNA expression and protein release in HTR-8/SVneo, similarly to endothelial cells. The cellular mechanism involved HIFα. BeWo responded to representative agents similarly to human primary placental tissues in the literature. These data support that the BeWo-hypoxia model mimics a key pathogenic mechanism of preeclampsia and has potential value for translational drug discovery.


Duodenal nonheme iron content correlates with iron stores in mice, but the relationship is altered by Hfe gene knock-out.
Hereditary hemochromatosis is a common iron-loading disorder found in populations of European descent. It has been proposed that mutations causing loss of function of HFE gene result in reduced iron incorporation into immature duodenal crypt cells. These cells then overexpress genes for iron absorption, leading to inappropriate cellular iron balance, a persistent iron deficiency of the duodenal mucosa, and increased iron absorption. The objective was to measure duodenal iron content in Hfe knock-out mice to test whether the mutation causes a persistent decrease in enterocyte iron concentration. In both normal and Hfe knock-out mice, duodenal nonheme iron content was found to correlate with liver iron stores (P <.001, r = 0.643 and 0.551, respectively), and this effect did not depend on dietary iron levels. However, duodenal iron content was reduced in Hfe knock-out mice for any given content of liver iron stores (P <.001).


Open tibial fractures treated with the Ex-fi-re external fixation system.
Fifty open tibial fractures were treated with the Ex-fi-re external fixation system from 1987 to 1994. According to the Gustilo and Anderson classification, there were 12 Grade I, 14 Grade II, 10 Grade IIIA, 13 Grade IIIB, and 1 Grade IIIC injuries. Eight fractures were segmental. The average patient patient age was 39 years (range, 16-85 years). With the reduction unit of the system, displaced tibial fractures could be reduced by the functions of the device in contrast to the manual reductions needed with other unilateral devices. Compression could be applied even to oblique fractures. The reductions were performed by this unit in all cases and were classified as exact in 28 of 41 cases. Exact reduction was defined as a reduction in which there was no more than 2 mm of translational displacement. The 8 segmental fractures were not classified according to reduction. Forty-three fractures healed with no secondary procedure. Three secondary bone graftings, 4 fibulotomies, and 3 renamed intramedullary fixations were performed in 6 patients. Thirty-two skin grafts were performed. There was 1 fracture site infection, and 1 curettage and 1 sequestrectomy were performed after union. At 1 year followup there were no signs of infection. Median time to union was 20 weeks, and median time to full unprotected weightbearing was 22 weeks. Fractures with an exact reduction had a median time of union of 19 weeks, compared with a median of 31 weeks in reductions with greater than 2 mm translational displacement. The exact reduction and translational compression applied in oblique fractures appeared to contribute to early consolidation.


Receptor-Ligand Binding Free Energies from a Consecutive Histograms Monte Carlo Sampling Method.
To obtain accurate and converged free energy calculations for ligand binding to biomolecular systems requires validated force fields and extensive sampling of the energy landscape, which requires exhaustive and effective conformational searching methods. Herein, we introduce the consecutive histograms Monte Carlo (CHMC) sampling protocol that generates receptor-ligand binding modes within a series of continuously distributed sampling units ranging from placement near the geometric center of the receptor's binding site to fully unbound states. This protocol employs independent energy-state sampling for calculating the ensemble energy within every predefined location along the receptor-ligand dissociation pathway, without the need to traverse the energy barriers as in molecular dynamic simulations during the dissociation procedure. We applied this method to a set of selected receptor targets with their corresponding ligands providing detailed studies of molecular binding free energy predictions. The results show that the CHMC gives an excellent accounting of the free energy surfaces and binding free energies at a reasonable computational cost.


Expression and functional properties of the Streptococcus intermedius surface protein antigen I/II.
Streptococcus intermedius is associated with deep-seated purulent infections. In this study, we investigated expression and functional activities of antigen I/II in S. intermedius. The S. intermedius antigen I/II appeared to be cell surface associated, with a molecular mass of approximately 160 kDa. Northern blotting indicated that the S. intermedius NCTC 11324 antigen I/II gene was transcribed as a monocistronic message. Maximum expression was seen during the early exponential phase. Insertional inactivation of the antigen I/II gene resulted in reduced hydrophobicity during early exponential phase, whereas no effect was detected during mid- and late exponential phases. Binding to human fibronectin and laminin was reduced in the isogenic mutant, whereas binding to human collagen types I and IV and to rat collagen type I was not significant for either the wild type or the mutant. Compared to the wild type, the capacity of the isogenic mutant to induce interleukin 8 (IL-8) release by THP-1 monocytic cells was significantly reduced. The results indicate that the S. intermedius antigen I/II is involved in adhesion to human receptors and in IL-8 induction.


ASK1 Regulates Bleomycin-induced Pulmonary Fibrosis.
Pulmonary fibrosis (PF) is an abnormal remodeling of cellular composition and extracellular matrix that results in histological and functional alterations in the lungs. Apoptosis signal-regulating kinase-1 (ASK1) is a member of the mitogen-activated protein (MAP) kinase family that is activated by oxidative stress and promotes inflammation and apoptosis. Here we show that bleomycin-induced PF is reduced in Ask1 knockout mice (Ask1-/-) compared with wild-type (WT) mice, with improved survival and histological and functional parameters restored to basal levels. In WT mice, bleomycin caused activation of ASK1, p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) in lung tissue, as well as changes in redox indicators (thioredoxin and heme-oxygenase-1), collagen content, and epithelial-mesenchymal transition markers (EMTs). These changes were largely restored toward untreated WT control levels in bleomycin-treated Ask1-/- mice. We further investigated whether treatment of WT mice with an ASK1 inhibitor, selonsertib (GS-4997), during the fibrotic phase would attenuate the development of PF. We found that pharmacological inhibition of ASK1 reduced activation of ASK1, p38, and ERK1/2 and promoted the restoration of redox and EMT indicators, as well as improvements in histological parameters. Our results suggest that ASK1 plays a central role in the development of bleomycin-induced PF in mice via p38 and ERK1/2 signaling. Together, these data indicate a possible therapeutic target for PF that involves an ASK1/p38/ERK1/2 axis.


The efficacy and tolerability of two novel H(1)/H(3) receptor antagonists in seasonal allergic rhinitis.
A therapeutic role for histamine H(3) receptor antagonism in allergic rhinitis has been proposed and may be complimentary to the well-known benefits of H(1) receptor antagonism. Combined H(1)/H(3) blockade has therefore been investigated as a novel therapeutic approach that may enhance symptom relief, particularly nasal blockage. Two novel H(1)/H(3) dual receptor antagonists were investigated in phase I and II safety and efficacy studies. One molecule (GSK1004723) was designed for intranasal administration as a suspension or solution and the other molecule (GSK835726) for oral administration. In phase I and II studies, both molecules were compared with an active control and/or placebo in randomised studies. In phase II studies, efficacy was assessed in an environmental allergen challenge chamber (ECC). Subjects with seasonal allergic rhinitis were exposed to allergen to induce symptoms. Efficacy and safety was measured over 4, 7 and 20-24 h post-dose. The endpoints included total nasal symptom score and nasal blockage. Intranasal suspension of GSK1004723 and oral GSK835726 were well tolerated. Single-dose intranasal suspensions of GSK1004723 (220, 1,100 μg) failed to demonstrate clinically significant attenuation of symptoms of allergic rhinitis induced in the ECC. Single (10, 50, 100 mg) and 3-day repeat (10 mg) dose oral GSK835726 demonstrated clinically significant attenuation of symptoms in the ECC comparable to cetirizine 10 mg. Three-day repeat dosing of the intranasal solution GSK1004723 1,000 μg also demonstrated a statistically significant attenuation of nasal symptoms, but was less than seen with cetirizine and GSK835726 and caused initial nasal discomfort. Combined H(1)/H(3) antagonism did not show differentiation from H(1) antagonism in reducing total nasal symptom score or nasal blockage.


Combined pulmonary fibrosis and emphysema: 3D time-resolved MR angiographic evaluation of pulmonary arterial mean transit time and time to peak enhancement.
To correlate conventional invasive pressure indexes of pulmonary circulation with pulmonary first-order arterial mean transit time (MTT) and time to peak enhancement (TTP) measured by means of three-dimensional time-resolved magnetic resonance (MR) angiography in patients with combined pulmonary fibrosis and emphysema (CPFE). The study was institutional review board approved. All subjects involved in the study provided written informed consent. Eighteen patients with CPFE were enrolled in this study. Thirteen healthy individuals matched for age and sex served as control subjects. Three-dimensional time-resolved MR angiography was performed by using a 3.0-T MR imager. Regions of interest (ROIs) were drawn manually on first-order pulmonary arteries. Within the ROIs, signal intensity-versus-time curves reflecting the first pass of the contrast agent bolus in the pulmonary vessels were obtained. MTT and TTP were calculated. Pulmonary arterial pressure and pulmonary capillary wedge pressure were measured with a double-lumen, balloon-tipped catheter that was positioned in the pulmonary artery. The mean pulmonary arterial pressure (mPAP) and the pulmonary vascular resistance (PVR) were determined. MTT and TTP values were prolonged significantly in patients with CPFE compared with those in the control subjects (P < .001). Mean TTP and mean MTT correlated directly with mPAP and PVR index (P < .005). At multiple linear regression analysis, MTT was the only factor independently associated with PVR index and mPAP. Three-dimensional time-resolved MR angiography enables determination of pulmonary hemodynamic parameters that correlate significantly with the pulmonary hemodynamic parameters obtained with invasive methods and may represent a complementary tool for evaluating pulmonary hypertension in patients with CPFE.


Turbo-PUVA: dihydroxyacetone-enhanced photochemotherapy for psoriasis: a pilot study.
Dihydroxyacetone (DHA), a colorless sugar in "sunless" tanning lotions, binds to stratum corneum to form a UV-A-protective brown pigment. Bound DHA polymer is shed faster from hyperproliferative skin sites such as psoriatic plaques. We tested the hypothesis that selective shedding of DHA pigment during psoralen-UV-A (PUVA) treatment of psoriasis may allow higher UV-A doses, thus accelerating clearing while protecting uninvolved skin. Concurrent use of lactic acid was investigated as an aid in removing scale and residual DHA from psoriatic plaques. Thirty psoriatic patients with more than 20% body surface area involvement were recruited. The 6 PUVA study groups were (1) standard American style, (2) American style plus lactic acid, (3) DHA-PUVA or "topical ultraviolet-resisting barrier to optiimize PUVA" (Turbo-PUVA), (4) Turbo-PUVA with lactic acid, (5) European style, and (6) European style plus DHA. Combinations of lactic acid and European-style treatment were not studied. Each subject received up to 30 oral PUVA treatments twice weekly 3 days apart. The DHA-PUVA groups used 15% DHA lotion twice weekly. Lactic acid groups used 7% lotion daily except on treatment days. Psoriasis area and severity index scores were recorded weekly. Turbo-PUVA allowed higher UV-A exposures with minimal burns, showed faster clearing, and required fewer treatments for 90% clearing (P<.001). Protection of uninvolved skin by DHA during PUVA treatment allows higher UV-A exposures to be tolerated, demonstrates faster clearing, and requires fewer treatments to clear psoriasis. By reducing the total body dose received, Turbo-PUVA may also reduce long-term risks.


Different islet protein expression profiles during spontaneous diabetes development vs. allograft rejection in BB-DP rats.
Type 1 diabetes (T1D) is characterized by selective autoimmune destruction of the insulin producing beta-cells in the islets of Langerhans. When the beta-cells are destroyed exogenous administration of insulin is necessary for maintenance of glucose homeostasis. Allogeneic islet transplantation has been used as a means to circumvent the need for insulin administration and has in some cases been able to restore endogenous insulin production for years. However, long life immunosuppression is needed to prevent the graft from being rejected and destroyed. Changes in protein expression pattern during spontaneous diabetes development in the diabetes prone BioBreeding rat (BB-DP) have previously been described. In the present study, we have investigated if any of the changes seen in the protein expression pattern during spontaneous diabetes development are also present during allograft rejection of BB-DP rat islets. Two hundred neonatal islets were syngeneically transplanted under the kidney capsule of 30 day old BB-DP rats and removed prior to and at onset of diabetes. Allogeneically transplanted islets from BB-DP rats were removed before onset of allograft rejection and at maximal islet graft inflammation (rejection). The protein expression profiles of the transplants were visualised by two-dimensional gel (2-DG) electrophoresis, analysed and compared. In total, 2590 protein spots were visualised and of these 310 changed expression (p < 0.01) in syngeneic islet transplants in the BB-DP rats from 7 days after transplantation until onset of diabetes. In BB-DP islets transplanted to WK rats 53 protein spots (p < 0.01) showed changes in expression when comparing islet grafts removed 7 days after transplantation with islet grafts removed 12 days after transplantation where mononuclear cell infiltration is at its maximum. Only four protein spots (1%) were significantly changed in both syngeneic (autoimmune) and allogeneic islet destruction. When comparing protein expression changes in syngeneic BB-DP islet transplants from 37 days after transplantation to onset of diabetes with protein expression changes in allografts from day 7 to 12 after transplantation only three spot were found to commonly change expression in both situations. In conclusion, a large number of protein expression changes were detected in both autoimmune islet destruction and allogeneic islet rejection, only two overlaps were detected, suggesting that autoimmune islet destruction and allogeneic islet rejection may result from different target cell responses to signals induced by the cellular infiltrate. Whether this reflects activation of distinct signalling pathways in islet cells is currently unknown and need to be further investigated.


[Hepatitis A virus mimotope mapping by phage display peptide library].
A 12 mer phage display peptide library was used to identify hepatitis A virus mimotopes of antigenic determinants, to provide the feasibility of virus epitope mapping by using this approach. Using purified anti-hepatitis A virus monoclonal antibody as affinity selective molecule, phage display peptide library was biopanned and positive clones were selected by ELISA, competition assay and DNA sequencing. 10 ELISA positive clones were chosen for DNA sequencing, and the displayed peptide sequences were deduced. 9 of them showed identical nucleotide sequence, and similarity in their amino acid sequence with VP1 of HAV HM175 was found, but no sequence homology was found between the other phage clone and the capsid proteins of HAV. Those peptides may behave as mimotopes of HAV. The mimotope of HAV was selected by using phage display peptide library screening. The results provide the potential of this method to search for the mimotopes of the virus.


[Observation on therapeutic effects of scraping therapy and warming acupuncture-moxibustion on 50 cases of fasciitis of back muscles].
To search for the best method for treatment of fasciitis of back muscles. One hundred cases of fasciitis of back muscles were randomly divided into two groups. The treatment group of 50 cases were treated with scraping and warming acupuncture and moxibustion at Fengmen (BL 12), Feishu (BL 13), Quyuan (SI 13), Bingfeng (SI 12), Jiafeng, local pressure pain points, and cord-like node; and the control group of 50 cases with simple acupuncture. In the treatment group, 40 cases were cured and 10 cases improved with a total effective rate of 100.0%; in the control group, 26 cases were cured and 16 cases improved, 8 cases were ineffective with a total effective rate of 84.0%. The treatment group in improvement of pressure pain and pain was better than the control group, with scores significantly decreased (P < 0.01). Scraping therapy and warming acup-moxibustion have obvious effect on fasciitis of back muscles, and it is a better therapy for this disease.


Physical activity patterns in patients with early and late age-related macular degeneration.
Age-related macular degeneration (AMD) leads to visual impairment that affects visual functioning and thereby the ability to be physically active. We investigated physical activity patterns in patients with AMD. Patients with early and late AMD and elderly controls were recruited for this hospital-based cross-sectional study. All participants had their best-corrected visual acuity measured and were interviewed about their physical activity based on questions that covered regular physical activity, physical activity that would work up sweat, climbing the stairs and time spent on walking outdoors. We recruited 198 participants of whom 196 were eligible for inclusion in the analyses (68 controls, 25 with early AMD and 103 with late AMD). The frequency of regular physical activity did not differ between patients with early and late AMD and elderly controls. Lower best-corrected visual acuity in the best-seeing and the worse-seeing eye was associated with less engagement in physical activities that would work up sweat and a lower number of steps taken daily. Patients with bilateral vision loss from late AMD engaged in physical activities that were more controlled and less demanding of sharp central vision. Patients with late AMD may still be physically active even when the disease progresses and vision is lost, but activities may change into more controlled and less central vision-demanding ones. The Lundbeck Foundation. not relevant.


Human anterior pituitary's ACTH cells during the aging process: immunohistochemic and morphometric study.
Corticotrophs produce a hormone that stimulates the adrenal gland cortex to secrete glucocorticoids, which in turn have effects on carbohydrate and protein metabolism. Quantification, morphological characteristics, and distribution of corticotrophs in the anterior pituitary and changes in the number and shape of the cells during aging have been examined using immunohistochemical and morphometric methods. The material consisted of 14 anterior pituitaries taken from cadavers at routine autopsy. The tissue was processed by standard histological procedure and the obtained slices were stained by the monoclonal anti-ACTH antibody for corticotrophs identification. Digital images of stained histological sections were analyzed using the morphometric method with the Image J system. The volume density of ACTH positive cells was determined. The cases were classified into three age groups. One-way ANOVA showed that the volume density of the corticotrophs was significantly higher in the second and third group in relation to the first group. The difference in the volume densities of the corticotrophs between the genders was not significant. Morphometric and statistical analyses demonstrated a significant positive correlation between the corticotrophs volume densities and the age of the evaluated cases. Linear regression showed that age significantly predicts corticotrophs volume density. Corticotrophs significantly increase during the life span.


Diagnosis of gestational diabetes mellitus: can we avoid the glucose challenge test?
To identify risk factors for gestational diabetes mellitus (GDM) in patients who had either a normal or abnormal glucose tolerance test (GTT) after failing the initial glucose challenge test (GCT). If identified, consideration can be given to circumvent the glucose challenge test for those at risk. A chart review was performed on 557 patients with abnormal GCT, 278 had an abnormal GTT (cases), and 279 had normal GTT (controls). The following risk factors were extracted: patients' age, body mass index (BMI), ethnicity, selected personal history, and family history. A primary logistic regression and secondary exploratory logistic regression were used to analyze the data. Of the risk factors reviewed age, BMI, and prior history of GDM were predictive of GDM in the current pregnancy. Age 30-34 had an odds ratio (OR) of 1.95, 95% confidence interval (CI) [1.25,3.05] and over 35 had an OR 3.87 CI [2.12,7.05]. BMI over 30 had an OR 1.95, CI [1.25,3.05] and prior GDM had an OR 2.82 CI [1.55,5.13]. The combination of age and BMI had a significant OR, but not a significant increase over individual risk factors. Screening by risk factors to circumvent glucose challenge testing may cause unnecessary testing and cost.


Time-resolved phase measurement of a self-amplified free-electron laser.
We report on the first time-resolved phase measurement on self-amplified spontaneous emission (SASE) free-electron laser (FEL) pulses. We observed that the spikes in the output of such free-electron laser pulses have an intrinsic positive chirp. We also observed that the energy chirp in the electron bunch mapped directly into the FEL output. Under certain conditions, the two chirps cancel each other. The experimental result was compared with simulations and interpreted with SASE theory.


Pharmacological Modulation of Smooth Muscles and Platelet Aggregation by Psidium cattleyanum.
Traditionally, in the Southern Asian countries, Psidium cattleyanum is a widely used plant for the management of various ailments such as gastrointestinal, respiratory, and cardiac disorders, but it lacks proof on a scientific basis, and therefore, this is the major emphasis of the current research work. Crude extract of Psidium cattleyanum (Pc.Cr) was preliminary analyzed for the presence of different classes of bioactive molecules. The aqueous and dichloromethane fractions of Pc.Cr were subjected to in vitro and in vivo studies. It was applied at variable concentrations (0.1-10 mg/ml) to isolated rabbit jejunum to investigate spasmolytic effect. Concentration dependent curves of calcium were constructed to check the calcium channel antagonistic activity. For the evaluation of tracheorelaxant activity, isolated tracheal tissue was treated with High-K+ (80 mM) and carbachol (CCh) and then challenged cumulatively with Pc.Cr. To study the antidiarrheal effect of the plant extract, castor oil-induced diarrhea model was adopted. For evaluation of the hypotensive effect of Pc.Cr, it was given intravenously to preanesthetized normotensive rats, and the response was recorded using pressure transducer. Platelet rich plasma was used for the assessment of the antiplatelet activity when challenged with purinergic and adrenergic agonists. Concentration-dependent inhibition of spontaneous and High-K+ mediated contractions in isolated jejunum was observed by the application of Pc.Cr. Contractions induced in isolated tracheal tissue by High-K+ and CCh were inhibited by application of Pc.Cr to these tissues. Similarly, application of Pc.Cr to High-K+ and phenylephrine (PE) treated aortic strips resulted in vasodilation. Platelet aggregation inhibition was shown by Pc.Cr against adenosine diphosphate (ADP) only. The antidiarrheal effect was observed as a reduction in the total number of feces in Pc.Cr-treated mice when given castor oil. Dose-dependent hypotension was seen in normotensive rats when treated with Pc.Cr intravenously. This study showed the spasmolytic, tracheorelaxant, vasodilator, platelet aggregation inhibitory, antidiarrheal, and hypotensive activities of P. cattleyanum which may be due to the blockage of calcium channels, but the involvement of any other pathway cannot be ignored.


[Anesthetic management with ATP for endovascular thoracic aortic repair].
A 78-year-old man with thoracic aortic aneurysm was scheduled for endovascular stent-graft surgery without cardiopulmonary bypass. He had a history of myocardial infarction five months before and echocardiography revealed ejection fraction of 37%. Deployment of the stent-graft was performed during third degree atrioventricular (A-V) block of 32 seconds produced by adenosine 5'-triphosphate (ATP) 30 mg. There were no complications during this procedure. ATP is a convenient and suitable agent to produce transient A-V block for the precise deployment of the stent-graft in these patients with severe cardiopulmonary complications.


Cytokine-induced chromatin modifications of the type I collagen alpha 2 gene during intestinal endothelial-to-mesenchymal transition.
Fibrosis of the intestine is currently an irreversible complication of inflammatory bowel disease; yet, little is understood of the underlying pathogenesis and antifibrotic strategies remain elusive. To develop effective therapies, knowledge of the mechanism of transcription and excessive deposition of type I collagen, a hallmark of fibrosis, is needed. We have shown previously that endothelial-to-mesenchymal transition (EndoMT) contributes to the pool of intestinal fibrotic cells and that a cytokine cocktail (interleukin 1-β, tumor necrosis factor α, and transforming growth factor β) induces collagen I alpha 2 (COL1A2) mRNA and protein. Chromatin immunoprecipitation assays on pure cultures of human intestinal mucosal endothelial cells undergoing EndoMT were performed with antibodies to specific histone modifications and RNA polymerase II. Reverse transcriptase-PCR was used to quantify the levels of Col1A2 and endothelial-specific von Willebrand factor (vWF) mRNA. We showed that cytokines induce selective chromatin modifications (histone 4 hyperacetylation, and hypermethylation of histone 3) and phosphorylated RNA polymerase II at the COL1A2 promoter. Hypoacetylated and hypomethylated histone 3 was detected on the repressed vWF gene. Prolonged exposure to cytokines (16 days) retained hyperacetylation of select lysines in H4 on the COL1A2 promoter. Removal of cytokines after 16 days and continued culture for 10 days showed persistent hyperacetylation at lysine 16 in histone H4. This is the first study to show that COL1A2 gene expression is associated with cytokine-induced, temporally ordered, and persistent chromatin modifications and suggests that these are important determinants of gene expression in EndoMT and intestinal fibrosis.


Susceptibility of a cell line derived from the kidney of Chinese rice-field eel, Monopterus albus to the infection of rhabdovirus, CrERV.
Chinese rice-field eels rhabdovirus (CrERV), belonging to the genus Perhabdovirus in the family Rhabdoviridae, is the causative agent of the haemorrhagic disease of Chinese rice-field eels, Monopterus albus. The present study aims to establish a cell line derived from the kidney of Chinese rice-field eel (CrEK) for the further study of the pathogenic virus. CrEK cells were epithelioid-like and grew well in M199 medium supplemented with 10% foetal bovine serum at 28°C, and the cell line has been subcultured for more than 80 times. Karyotyping analysis of CrEK cells at 25th passage indicated a modal chromosome number of 24. Significant cytopathic effect (CPE) was observed in CrEK cells after infection with CrERV, and the virus titre reached 107.8 ± 0.45 TCID50 /mL. The transmission electron microscopy revealed that there were a large number of virus particles in the cytoplasm of cells. The virus infection in cells was also assayed by using indirect immunofluorescence assay (IFA), fluorescence in situ hybridization (FISH), reverse transcription PCR (RT-PCR) and quantitative real-time reverse transcription-PCR (qRT-PCR). In experimental infection, CrERV cultured by cells could cause over 90% mortality in fish. CrEK represents the first kidney cell line originated from Chinese rice-field eels and be a potential material for investigating the mechanism of virus infection in this fish and the control methods for the disease.


A developing world perspective on homicide and personality disorder.
High rates of psychotic disorder among special populations of homicide offenders, females, youth and the mentally disordered, have received much investigation. Personality disorder, especially antisocial personality disorder, augments the relative risk ratio of violence, especially in combination with substance use disorder. Few studies of these correlates of violence and especially homicide have been reported in low- and medium-income countries (LMIC). Using the structured clinical interview for DSM diagnosis (SCID), personality disorders were identified in a cross sectional study involving 546 homicide offenders in Jimma prison, Ethiopia. Predictors of personality disorder were determined using multivariate analysis of various demographic and clinical variables, for example, age, psychiatric history and substance use. Out of the 316 offenders who completed the SCID, only 16% fulfilled DSM IV criteria for personality disorder. The rationale for killing, self-defence, anger and revenge (52% of offenders), planning involved in offending (50%) and reasonably high level of relationship functioning (57% married) were different from most data from the high-income countries. Diagnostically relevant cultural factors in LMIC, not in play in high-income countries, may explain the differences in personality disorders similar to other mental disorders and the underlying mediators of homicide.


Protective effect of systemic administration of erythropoietin on auditory brain stem response and compound action potential thresholds in an animal model of cochlear implantation.
An animal model of cochlear implantation has been developed, and the hearing threshold was evaluated after different surgical procedures. The effect of perioperative systemic administration of erythropoietin on the hearing loss induced by cochlear implantation was tested. Twenty-nine guinea pigs with normal hearing underwent implantation of a 254-microm-diameter array through a cochleostomy. The effects on hearing of cochleostomy and transient and long-term array implantation (21 days) were assessed by testing of the auditory brain stem responses and compound action potentials. Eleven implanted animals received intraperitoneal administration of erythropoietin. Selected computed tomographic scans and cochlear histologic studies were performed 1 month after implantation to confirm proper placement of the array. The erythropoietin concentration at the time of surgery was assessed in samples of perilymph, cerebrospinal fluid, and blood. The cochleostomy and transient array insertion had no effect on hearing thresholds. Long-term array implantation induced a stable decrease of hearing threshold (30 dB), a decrease that was reduced by 12 dB in erythropoietin-treated animals. The erythropoietin-treated animals had better hearing preservation at higher frequencies. Fibrosis surrounding the array was seen in both groups. The hearing loss observed was probably due to the presence of the array in the cochlea. The intraperitoneal injection of erythropoietin improved the hearing threshold shift induced by implantation.


Dual-sided lithography: a method for evaluating alignment accuracy.
We describe a method for measuring the accuracy of aligners used to align lithographic patterns on opposite sides of a substrate (back-to-front aligners). The method, with minor modifications, can also be used as an aid in performing back-to-front alignments. The method is based on interferometric principles, is insensitive to manufacturing errors, and is simple to implement. The version described in this paper is fabricated by using binary optics technology and can measure the accuracy of aligners to +/-0.2 microm.


A study on allergen sensitivity in patients with allergic rhinitis in Bangalore, India.
Allergic rhinitis is the most common form of non-infectious rhinitis, affecting 500 million people worldwide, with one-fifth of those affected living in the Indian subcontinent. The skin prick test is the most valuable test for detecting offending allergens, and can be helpful for patient education, allergen avoidance and immunotherapy planning. The skin prick test was performed with 49 allergens in 486 patients who presented with symptoms of allergic rhinitis, and the allergen profile was studied. Of the 486 allergic rhinitis patients, 335 (68.93 per cent) showed allergen positivity to the skin prick test. Dust mite was the most common allergen, with positive results in 44.65 per cent of cases. The most common offending allergen in our study was the dust mite. Identification of specific allergens for a particular geographical area aids patient education and enables allergen-specific immunotherapy.


Identification of regulatory modules by co-clustering latent variable models: stem cell differentiation.
An important issue in stem cell biology is to understand how to direct differentiation towards a specific cell type. To elucidate the mechanism, previous studies have focused on identifying the responsible gene regulators, which have, however, failed to provide a systemic view of regulatory modules. To obtain a unified description of the regulatory modules, we characterized major stem cell species by employing a co-clustering latent variable model (LVM). The LVM-based method allowed us to elucidate the cell type-specific transcription factors, using genomic sequences as well as expression profiles. We used a list of genes enriched in each of 21 stem cell subpopulations, and their upstream genomic sequences. The LVM-based study allowed us to uncover the regulatory modules for each stem cell cluster, e.g. GABP and E2F for the proliferation phase, and Ap2alpha and Ap2gamma for the quiescence phase. Furthermore, the identities of the stem cell clusters were well revealed by the constituent genes that were directly targeted by the modules. Consequently, our analytical framework was demonstrated to be useful through a detailed case study of stem cell differentiation and can be applied to problems with similar characteristics.


Formation of macromolecular complexes and other effects of DNA treatment with diethyl and dimethyl sulfate: physico-chemical and electron microscopic studies.
In vitro exposures of isolated DNA to one of the two carcinogenic and mutagenic chemicals, diethylsulfate or dimethylsulfate, induces several kinds of physicochemical and morphological alterations. These changes are detectable by a variety of independent techniques. A fraction of DNA treated briefly with either of these two chemicals moves during velocity centrifugation experiments less rapidly than the bulk of control DNA and more rapidly through gels during electrophoresis. This apparent decrease in size is paralleled by the formation of large DNA aggregates with mobilities indicating molecular weights several times that of the untreated, control DNA. The presence of a basic protein in the incubation mixture increases the rate of formation of such complexes. the tendency of the alkylated DNA to bind to both biological and non-biological materials is reflected in the increased attachment of DNA to columns built with methyl-esterified serum albumin and in its quantitative retention on nitrocellulose filters. DNA exposed to dimethylsulfate decreases its density in CsCl gradients. A mixture of two or more DNAs of different densities exposed to this chemical produces an u.v.-absorbing band which is found in such gradients at an intermediate density. If the alkylation reaction is carried out in the presence of a protein, a portion of DNA bands at a density intermediate between the density of DNA and that of the protein, even in the presence of an ionic detergent in the gradient. Under the electron microscope the alkylated DNA shows multiple single-strand breaks and peeling-off whiskers of denatured DNA. Aggregates of DNA molecules become visible upon further incubation of DNA with the alkylating agent. We suggest that the DNA-DNA and DNA- protein complexes play an important role in the process of carcinogenesis and mutagenesis.


Automated solid-phase extraction with high-performance liquid chromatography analysis of pyridinium crosslinks.
An automated solid-phase extraction procedure for free and total pyridinium crosslinks in urine, with on-line HPLC analysis, is described. The pyridinium crosslinks either following hydrolysis in 3 M HCl or free in urine were extracted using a Gilson Aspec system onto extraction cartridges containing an octasilane/cation-exchanger sorbent. After washing, the crosslinks were eluted with 400 microl 100 mM sodium formate, pH 5, and 50 microl was automatically injected onto the analytical HPLC column. Detection was by fluorescence (Ex 295 nm, Em 400 nm). Recoveries were 95-100% with a limit of quantitation (s/n = 5) of 1.97 nmol/liter (nM) for pyridinoline and 2.79 nM for deoxypyridinoline. The interassay coefficient of variation was 6.5% for pyridinoline and 8.2% for deoxypyridinoline. The throughput of the system was up to 70 samples per day. The method correlated well with the established manual cellulose extraction but was substantially simpler and more reliable. A good correlation with an immunoassay for deoxypyridinoline was also obtained.


Approximate profile likelihood estimation for Cox regression with covariate measurement error.
In nutritional epidemiology, measurement error in covariates is a well-known problem since dietary intakes are usually assessed through self-reporting. In this article, we consider an additive error model in which error variables are highly correlated, and propose a new method called approximate profile likelihood estimation (APLE) for covariates measured with error in the Cox regression. Asymptotic normality of this estimator is established under regularity conditions, and simulation studies are conducted to examine the finite sample performance of the proposed estimator empirically. Moreover, the popular correction method called regression calibration is shown to be a special case of APLE. We then apply APLE to deal with measurement error in some nutrients of interest in the EPIC-InterAct Study under a sensitivity analysis framework.


Sleep-disordered breathing: in depression and schizophrenia.
Sleep disorders are becoming more prevalent. There is an overlap of symptoms related to obstructive sleep apnea syndrome (OSAS) and many psychiatric conditions. Complaints of excessive sleepiness, insomnia, cognitive dysfunction, and depressive symptoms can be related to both disease states. Obstructive sleep apnea syndrome is characterized by repetitive disruption of sleep by cessation of breathing and was first described in the 19th century by bedside observation during sleep. Physicians observed this cessation of breathing while the patient slept and postulated that these episodes were responsible for subsequent complaints of sleepiness. OSAS can coexist with major depressive disorder, exacerbate depressive symptoms, or be responsible for a large part of the symptom complex of depression. Additionally, in schizophrenia, sleep apnea may develop as a result of chronic neuroleptic treatment and its effect on gains in body weight, a major risk factor for the development of OSAS.It is important to recognize the signs and symptoms of sleep apnea, namely excessive daytime sleepiness, snoring, and witnessed apneas. Recognition of the existence of sleep apnea, prompt referral to a sleep specialist, and ultimately treatment of an underlying sleep disorder, such as OSAS, can ameliorate symptoms of psychiatric disease.


Complementarity of SOMAscan to LC-MS/MS and RNA-seq for quantitative profiling of human embryonic and mesenchymal stem cells.
Dynamic range limitations are challenging to proteomics, particularly in clinical samples. Affinity proteomics partially overcomes this, yet suffers from dependence on reagent quality. SOMAscan, an aptamer-based platform for over 1000 proteins, avoids that issue using nucleic acid binders. Targets include low expressed proteins not easily accessible by other approaches. Here we report on the potential of SOMAscan for the study of differently sourced mesenchymal stem cells (MSC) in comparison to LC-MS/MS and RNA sequencing. While targeting fewer analytes, SOMAscan displays high precision and dynamic range coverage, allowing quantification of proteins not measured by the other platforms. Expression between cell types (ESC and MSC) was compared across techniques and uncovered the expected large differences. Sourcing was investigated by comparing subtypes: bone marrow-derived, standard in clinical studies, and ESC-derived MSC, thought to hold similar potential but devoid of inter-donor variability and proliferating faster in vitro. We confirmed subtype-equivalency, as well as vesicle and extracellular matrix related processes in MSC. In contrast, the proliferative nature of ESC was captured less by SOMAscan, where nuclear proteins are underrepresented. The complementary of SOMAscan allowed the comprehensive exploration of CD markers and signaling molecules, not readily accessible otherwise and offering unprecedented potential in subtype characterization. Mesenchymal stem cells (MSC) represent promising stem cell-derived therapeutics as indicated by their application in >500 clinical trials currently registered with the NIH. Tissue-derived MSC require invasive harvesting and imply donor-to-donor differences, to which embryonic stem cell (ESC)-derived MSC may provide an alternative and thus warrant thorough characterization. In continuation of our previous study where we compared in depth embryonic stem cells (ESC) and MSC from two sources (bone marrow and ESC-derived), we included the aptamer-based SOMAscan assay, complementing LC-MS/MS and RNA-seq data. Furthermore, SOMAscan, a targeted proteomics platform developed for analyzing clinical samples, has been benchmarked against established analytical platforms (LC-MS/MS and RNA-seq) using stem cell comparisons as a model.


Off-site primary percutaneous coronary intervention in a new centre is safe: comparing clinical outcomes with a hospital with surgical backup.
To evaluate the procedural and clinical outcomes of a new primary percutaneous coronary intervention (PPCI) centre without surgical back-up (off-site PCI) and to investigate whether these results are comparable with a high volume on-site PCI centre in the Netherlands. Controversy remains about the safety and efficacy of PPCI in off-site PCI centres. We retrospectively analysed clinical and procedural data as well as 6‑month follow-up of 226 patients diagnosed with ST-elevated myocardial infarction (STEMI) who underwent PPCI at VieCuri Medical Centre Venlo and 115 STEMI patients who underwent PPCI at Catharina Hospital Eindhoven. PPCI patients in VieCuri Medical Centre had similar procedural and clinical outcomes to those in Catharina Hospital. Overall there were no significant differences. The occurrence of procedural complications was low in both groups (8.4 % VieCuri vs. 12.3 % Catharina Hospital). In the VieCuri group there was one procedural-related death. No patients in either group needed emergency surgery. At 30 days, 17 (7.9 %) patients in the VieCuri group and 9 (8.1 %) in the Catharina Hospital group had a major adverse cardiac event. Performing PPCI in an off-site PCI centre is safe and effective. The study results show that the procedural and clinical outcomes of an off-site PPCI centre are comparable with an on-site high-volume PPCI centre.


Familial presenile dementia with CJD-like lesions: preliminary results.
A case of an unknown type of familial presenile dementia is reported. The patient was a 56-year-old female, whose main clinical symptom was a gradually progressive dementia over 16 years. She had no myoclonus or periodic synchronous discharge in the EEG. The CT scans revealed marked cerebral atrophy with prominent atrophy of the cerebral white matter. One of her sisters is thought to suffer from the same disease, and is now in an apallic state. The patient was clinically diagnosed as having familial Alzheimer's disease. The neuropathological features consisted of severe cerebral cortical degeneration with conspicuous proliferation of gemistocytic astrocytes as well as severe cerebral white matter degeneration. These cerebral lesions are most similar to those of the panencephalopathic type of Creutzfeldt-Jakob's disease (CJD). However, our case differs from it in that the cerebellar degeneration was very mild. Transmission experiments of frozen tissue from the patient into animals are being tried. The neurochemical data suggested cholinergic deficits. As far as we know, such a case has never been reported in the literature.


Evaluation of three sampling methods for the microbiological analysis of broiler carcasses after immersion chilling.
Countries have different official programs and implement different sampling methods for the detection of Salmonella on poultry carcasses. In Brazil, a 25-g sample of skin and muscle excision (SME) from the wings, neck, and pericloacal parts is used; in the European Union (EU), a 25-g sample of neck skin (NSE) is used; and, in the United States, the whole carcass is rinsed with 400 ml of diluent (WCR). In the present study, these methods were evaluated to compare Salmonella occurrence and counts of hygiene indicator microorganisms (Escherichia coli, Enterobacteriaceae, and total viable count of aerobic mesophilic bacteria) using different carcasses from the same flock and also using different analytical units taken from the same carcass. Eighty flocks, with four broiler carcasses from each, were included in this study; three broilers were sampled according to protocols from Brazil, the EU, and the United States, and the last one by all three methods. SME, NSE, and WCR provided equivalent results (P > 0.05) for Salmonella detection on broiler carcasses when using different carcasses from the same flock and when using the same carcass. The predominant serovar was Salmonella Enteritidis. For the enumeration of hygiene indicator microorganisms, WRC provided higher counts than SME or NSE (P < 0.05), when using both the same or different carcasses. Therefore, it is possible to directly compare Salmonella results in poultry carcasses when using the methods recommended by the legislative bodies of Brazil, the United States, and the EU. However, WCR provides the best results for hygiene indicator microorganisms.


Thermal Destruction of Escherichia coli and Klebsiella pneumoniae in Human Milk.
A continuous flow high-temperature short-time pasteurization system was used to determine kinetic parameters (D- and z-values) for thermal destruction of the bacterial pathogens, Escherichia coli and Klebsiella pneumoniae , in mature human milk. D-and z-alues of each bacterium were determined from data on survivors enumerated on both selective media, Violet Red Bile agar or MacConkey's, and on a non-selective medium, nutrient agar (NA). For E. coli , D-values were determined at 58, 60, 62 and 64°C. The predicted value of D at 60°C is 31.5 s. The z-value for E. coli is 3.2°C. D-values for K. pneumoniae were determined at 52, 56 and 58°C. Based on these data the predicted value of D at 60°C is 1.3 s. The z-value for K. pneumoniae , is 2.8°C. For both E. coli and K. pneumoniae , counts on NA tend to be higher than on selective media. This is undoubtedly due to the inhibitory nature of the selective media. This also suggests that some degree of thermal injury may occur for each organism.


Helpfulness and the development of competence in adolescence.
Using data from a representative panel of 1,000 Minnesota youth, this paper explores "helpfulness" in 2 spheres of adolescents' lives: the home and paid work settings. We examine the social structural conditions under which helpful behaviors are elicited, the interrelations of helpfulness and competence across 2 years of middle adolescence, and whether social circumstances moderate the effects of helpfulness on competence. Both boys' and girls' helpfulness in the home is responsive to family need. Furthermore, helpfulness at work and girls' competence are reciprocally related. We find evidence that the effects of helpfulness depend on the helper's motivations and the act's meaning, as shaped by the social context. Girls' competence is diminished by helpfulness in the home under conditions of poor father-daughter relationships and coercive maternal control.


[Conservative therapy of backache. Part 4: Manual therapy].
The literature on the clinical effectiveness of manipulation in low back pain is extensive, although scientific studies that are free from flaws are much rarer. Most of the studies so far done show--with some reservations--a positive effect for manipulation. Given the proper indication, and with care being taken to observe contraindications, this modality can thus be recommended if performed by an experienced manipulator. However, this should not blind us to the fact that further investigations are necessary, and that the technique has no unequivocal advantages over exercise.


Trisomy 13 mosaicism.
Trisomy 13 is a chromosomal alteration with an incidence of 1 in 10,000 to 20,000 births. It can occur completely, partially or in mosaicism; the latter occurs when a percentage of cells are trisomic for chromosome 13, while the rest are euploid in an individual and corresponds to only 5% of all cases. Patients with trisomy 13 present a wide variable expressivity, ranging from severe malformations with early death (phenotype similar to the complete form and more frequent), to normal development and few dysmorphic findings. The clinical and cytogenetic findings of two new cases of trisomy 13 mosaicism are described. The importance of prenatal diagnosis, clinical findings, and interdisciplinary medical evaluation is highlighted, as well as an appropriate genetic counseling.


An object programming based environment for protein secondary structure prediction.
The most frequently used methods for protein secondary structure prediction are empirical statistical methods and rule based methods. A consensus system based on object-oriented programming is presented, which integrates the two approaches with the aim of improving the prediction quality. This system uses an object-oriented knowledge representation based on the concepts of conformation, residue and protein, where the conformation class is the basis, the residue class derives from it and the protein class derives from the residue class. The system has been tested with satisfactory results on several proteins of the Brookhaven Protein Data Bank. Its results have been compared with the results of the most widely used prediction methods, and they show a higher prediction capability and greater stability. Moreover, the system itself provides an index of the reliability of its current prediction. This system can also be regarded as a basis structure for programs of this kind.


Nonlytic Recombinant Phage Tail Fiber Protein for Specific Recognition of Pseudomonas aeruginosa.
Rapid and accurate bacterial detection is crucial to an early diagnosis for treating various infectious diseases. A recombinant tail fiber protein (P069) of the Pseudomonas aeruginosa ( P. aeruginosa) phage was expressed in Escherichia coli. After renaturation at a low temperature, the inclusion body of P069 was successfully transformed to an aqueous soluble protein that retained the capacity for recognizing P. aeruginosa. The recombinant P069 did not show lytic activity to P. aeruginosa, which facilitated the capture and manipulation of bacterial whole cells with a high flexibility for downstream identification and detection. Bioluminescent and fluorescent methods using this biorecognition element allowed P. aeruginosa detection with the detection limits of 6.7 × 102 CFU mL-1 and 1.7 × 102 CFU mL-1, respectively. Moreover, the specificity investigations showed that P069 was a species-specific protein. Therefore, it avoided the potential false negative results originating from the excessive high specificity of phage toward a given strain. It has been successfully applied to detect P. aeruginosa in spiked samples with acceptable recovery values ranging from 88% to 98%. The above results demonstrate that P069 is an ideal biorecognition element for the detection of P. aeruginosa in complicated sample matrixes.


Development of Candida-Specific Real-Time PCR Assays for the Detection and Identification of Eight Medically Important Candida Species.
Culture-based identification methods have been the gold standard for the diagnosis of fungal infection. Currently, molecular technologies such as real-time PCR assays with short turnaround time can provide desirable alternatives for the rapid detection of Candida microbes. However, most of the published PCR primer sets are not Candida specific and likely to amplify DNA from common environmental contaminants, such as Aspergillus microbes. In this study, we designed pan-Candida primer sets based on the ribosomal DNA-coding regions conserved within Candida but distinct from those of Aspergillus and Penicillium. We demonstrate that the final two selected pan-Candida primer sets would not amplify Aspergillus DNA and could be used to differentiate eight medically important Candida pathogens in real-time PCR assays based on their melting profiles, with a sensitivity of detection as low as 10 fg of Candida genomic DNA. Moreover, we further evaluated and selected species-specific primer sets covering Candida albicans, Candida glabrata, Candida tropicalis, and Candida dubliniensis and show that they had high sensitivity and specificity. These real-time PCR primer sets could potentially be assembled into a single PCR array for the rapid detection of Candida species in various clinical settings, such as corneal transplantation.


Synthesis and in vitro antimicrobial activity of 3-keto 16-membered macrolides derived from tylosin.
Several series of 14-membered ketolides derived from erythromycin exhibit useful antimicrobial activity against macrolide-resistant bacteria. To determine if 16-membered ketolides may possess analogous activity, 3-keto derivatives of 5-O-mycaminosyl-23-O-acetyltylonolide and desmycosin were synthesized by protection of susceptible functional groups, oxidation of the 3-hydroxyl group under modified Moffatt-Pfitzner conditions, and subsequent deprotection. The resulting 3-keto products unexpectedly adopted the 2,3-trans enol rather than the 3-keto tautomer. The trans configuration of the 2,3-double bond in the macrolide chain is most likely the result of hydrogen bond stabilization between the enol hydroxyl and lactone carbonyl, which places these two groups in a cis relationship. This preference for the enol tautomer in 16-membered macrolides is not seen with 14-membered ketolides. The in vitro antimicrobial activity of the enol derivatives was greatly reduced compared to their unoxidized parent compounds, but the reduced antimicrobial activity of the enol derivatives paralleled results from corresponding 2,3-anhydro derivatives of 16-membered macrolides, which also have 2,3-trans stereochemistry. These results are in contrast to those from 14-membered-ring macrolides in which 3-keto and 2,3-anhydro derivatives exhibit greater activity than 3-hydroxy compounds.


[Sclerotherapy of post-renal transplantation lymphocele with percutaneous instillation of amidotrizoate].
Incidence of post-renal transplant (RT) lymphocele varies between 0.6% to 41% depending on the author. Therapeutical management of these entities is controversial. (Open or laparoscopic) surgical marsupialization of the peritoneal cavity, percutaneous drainage, and percutaneous sclerosis with povidone-iodine are all valid options to treat post-RT lymphocele. This paper presents two cases of symptomatic post-RT lymphocele not suitable for laparoscopic treatment, which were resolved by intracavitary instillation of Sodium Amidotrizoate 76%. The first case had been previously treated with povidone-iodine with no resolution, also maintaining a 500 ml/24h deficit. In the second case, instillation with Sodium Amidotrizoate 76% was considered first choice approach. In both instances the lymphocele deficit ceased with instillation intervals of 6 and 14 days, respectively. In brief, percutaneous sclerosis with Amidotrizoate can be a valid alternative for the treatment of post-RT lymphocele.


Occurrence of ZZ/ZW sex chromosomes in Thoracocharax stellatus fish (Characiformes, Gasteropelecidae) from the Araguaia River, South America.
The karyotypic and chromosomal characteristics of the hatchetfish Thoracocharax stellatus from the Araguaia River, Brazil (Araguaia-Tocantins basin) were analyzed using Giemsa, AgNO(3), and CMA(3) fluorescent staining, and C-banding. The diploid chromosome number was 54 and the karyotypes of females and males were composed of six metacentrics, six submetacentrics, six subtelocentrics and 36 acrocentrics. Two unpaired acrocentric chromosomes were detected in the female karyotype. C-banding showed heterochromatic blocks at several chromosomes and an entirely heterochromatic acrocentric chromosome in females that was lacking in the male karyotype. This discovery indicated a heteromorphic sex chromosome system of the ZZ/ZW type. Ag-staining and CMA(3) fluorescence revealed one major chromosome pair bearing the NORs with the presence of additional signals in some metaphases. Both heterochromatic segments associated with Ag-NORs and the W chromosome were positively stained by CMA(3). Considering the present data and previous findings it is hypothesized that the occurrence of ZW sex chromosome system is widespread in the genus Thoracocharax.


Physical activity in individuals at risk for diabetes: Diabetes Prevention Program.
Leisure physical activity was assessed using questionnaires with different time frames in the Diabetes Prevention Program (DPP) cohort of 3234 overweight individuals aged > 25 yr with impaired glucose tolerance (IGT) from 27 centers across the United States. The three questionnaires were the Modifiable Activity Questionnaire (MAQ; past year), the Low-Level Physical Activity Recall (LOPAR; past 7 d), and the Third National Health and Nutrition Examination Survey (NHANES III; past month). This provided the opportunity to examine the relationship between the three activity measures and to compare activity levels of the DPP sample with that of a national sample with IGT. Leisure activity determined by the three questionnaires significantly correlated with each other, although the correlations between MAQ and NHANES III were stronger (men: rho = 0.52; women: rho = 0.49; P < 0.01) than between LOPAR and either measure (men: rho = 0.20 for MAQ, 0.24 for NHANES; women: rho = 0.10 for MAQ, 0.13 for NHANES). In the DPP, measures of obesity and glucose tolerance were significantly correlated with activity levels determined by MAQ and NHANES, but not LOPAR. Activity levels in DPP participants determined by the NHANES III questionnaire were generally higher than those reported by individuals meeting DPP eligibility criteria who were part of the NHANES cohort for similar age, body mass index, and race or ethnicity. If the DPP participants were more active than a national sample of individuals with IGT, this would have implications for translation when using the DPP lifestyle intervention in less active or less motivated populations. Finally, the weak relationship between activity levels obtained with MAQ and LOPAR may result from the fact that they encompass different time frames and different components of leisure activity.


Eflornithine treatment of refractory Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.
Eflornithine was offered as compassionate treatment of 33 episodes of Pneumocystis carinii pneumonia in 31 patients with acquired immunodeficiency syndrome who were intolerant of and/or unresponsive to conventional trimethoprim-sulfamethoxazole or pentamidine therapy. A full course of eflornithine consisted of ten days at 400 mg/kg/d but no more than 30 g/d in four divided intravenous doses, four days at 300 mg/kg/d in four divided intravenous doses, and then up to six weeks at 300 mg/kg/d in four divided oral doses where tolerated. Of 33 patient-episodes, 15 patients were discharged from the hospital without need for supplemental oxygen after receiving ten or more days of parenteral therapy and were classified as responders. Of the 16 episodes classified as treatment failures, death occurred within the first 10 days of therapy in 12, and supplemental oxygen could not be withdrawn in 4. The other two patients left the hospital without need of oxygen after receiving one and six days of treatment with eflornithine and were not considered evaluable for efficacy. The most serious adverse effect was thrombocytopenia, which occurred in 12 of 19 patients treated for ten days or more. Serious bleeding associated with thrombocytopenia was observed in two patients. Other common adverse effects were anorexia, nausea, and diarrhea. Prior to receiving eflornithine, 13 of 15 responders had received ten or more days of conventional therapy without demonstrating clinical improvement. Two had improved while receiving conventional therapy but were switched to eflornithine because of a treatment-limiting adverse effect of standard therapy. These results suggest that eflornithine may be useful as an alternative therapeutic agent for Pneumocystis carinii pneumonia. Studies designed to determine proper dosage, duration of therapy, and efficacy as primary therapy are warranted.


Effect of a Pragmatic, Cluster-randomized Controlled Trial on Patient Experience With Care: The Transforming Outcomes for Patients Through Medical Home Evaluation and reDesign (TOPMED) Study.
Health reform programs like the patient-centered medical home are intended to improve the triple aim. Previous studies on patient-centered medical homes have shown mixed effects, but high value elements (HVEs) are expected to improve the triple aim. The aim of this study is to understand whether focusing on HVEs would improve patient experience with care. Eight clinics were cluster-randomized in a year-long trial. Both arms received practice facilitation, IT-based reporting, and financial incentives. Intervention practices were encouraged to choose HVEs for quality improvement goals. To assess patient experience, 1597 Consumer Assessment of Healthcare Providers and Systems surveys were sent pretrial and posttrial to a stratified random sample of patients. Difference-in-difference multivariate analysis was used to compare patient responses from intervention and control practices, adjusting for confounders. The response rate was 43% (n=686). Nonrespondent analysis showed no difference between arms, although differences were seen by risk status and age. The overall difference in difference was 2.8%, favoring the intervention. The intervention performed better in 9 of 11 composites. The intervention performed significantly better in follow-up on test results (P=0.091) and patients' rating of the provider (P=0.091), whereas the control performed better in access to care (P=0.093). Both arms also had decreases, including 4 of 11 composites for the intervention, and 8 of 11 for the control. Practices that targeted HVEs showed significantly more improvement in patient experience of care. However, contemporaneous trends may have affected results, leading to declines in patient experience in both arms.