Analysis of FimX, a phosphodiesterase that governs twitching motility in Pseudomonas aeruginosa.
Type IV pili (Tfp) are polar surface structures of Pseudomonas aeruginosa required for twitching motility, biofilm formation and adherence. One protein required for the assembly of tfp is FimX, which possesses both GGDEF and EAL domains characteristic of diguanylate cyclases and phosphodiesterases respectively. In this work we demonstrate that FimX has phosphodiesterase activity towards bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), but does not show diguanylate cyclase activity. Instead, the imperfect GGDEF domain of FimX likely serves to activate phosphodiesterase activity when bound to GTP, as has recently been described for the Caulobacter crescentus composite GGDEF-EAL protein, CC3396. Bacteria expressing FimX in which either the GGDEF or EAL domain is deleted or mutated have phenotypes indistinguishable from a DeltafimX strain, demonstrating the importance of both domains to function. Previous work has shown that FimX localizes to the bacterial pole. In this work we show that restriction of FimX to a single pole requires intact GGDEF and EAL domains. Deletion of the amino-terminal REC domain of FimX, which contains a putative polar localization signal, results in a protein that still supports intermediate levels of pilus assembly and function. RFP-FimXDeltaREC, unlike RFP-FimX, is no longer localized to the bacterial pole, while transmission electron microscopy shows that surface pili can originate from non-polar sites in this mutant. Although DeltafimX mutants show limited in vitro cytotoxicity, they are as virulent as the wild-type strain in a murine model of acute pneumonia.


Statin therapy and lipoprotein(a) levels: a systematic review and meta-analysis.
Lipoprotein(a) [Lp(a)] is a causal and independent risk factor for cardiovascular disease (CVD). People with elevated Lp(a) are often prescribed statins as they also often show elevated low-density lipoprotein cholesterol (LDL-C) levels. While statins are well-established in lowering LDL-C, their effect on Lp(a) remains unclear. We evaluated the effect of statins compared to placebo on Lp(a) and the effects of different types and intensities of statin therapy on Lp(a). We conducted a systematic review and meta-analysis of randomized trials with a statin and placebo arm. Medline and EMBASE were searched until August 2019. Quality assessment of studies was done using Cochrane risk-of-bias tool (RoB 2). Mean difference of absolute and percentage changes of Lp(a) in the statin vs. the placebo arms were pooled using a random-effects meta-analysis. We compared effects of different types and intensities of statin therapy using subgroup- and network meta-analyses. Certainty of the evidence was determined using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Overall, 39 studies (24 448 participants) were included. Mean differences (95% confidence interval) of absolute and percentage changes in the statin vs. the placebo arms were 1.1 mg/dL (0.5-1.6, P < 0.0001) and 0.1% (-3.6% to 4.0%, P = 0.95), respectively (moderate-certainty evidence). None of the types of statins changed Lp(a) significantly compared to placebo (very low- to high-certainty evidence), as well as intensities of statin therapy (low- to moderate-certainty evidence). Statin therapy does not lead to clinically important differences in Lp(a) compared to placebo in patients at risk for CVD. Our findings suggest that in these patients, statin therapy will not change Lp(a)-associated CVD risk.


CT myocardial perfusion imaging: current status and future directions.
Computed tomography (CT) imaging of the heart has advanced rapidly, and it is now possible to perform a comprehensive assessment at a low radiation dose. CT myocardial perfusion imaging can provide additive information to CT coronary angiography, and is particularly useful in patients with heavily calcified coronary arteries or coronary artery stents. A number of protocols are now available for CT myocardial perfusion including static, dynamic, and dual-energy techniques. This review will discuss the current status of CT myocardial perfusion imaging, its clinical application, and future directions for this technology.


HLA-DQA1 and HLA-DQB1 genetic markers and clinical presentation in celiac disease.
Patients with celiac disease are diagnosed at any age and can exhibit a wide range of clinical manifestations. The reasons for this are unclear. The aim of this study was to investigate a possible correlation between the HLA-DQA1 and HLA-DQB1 genetic markers and clinical features of celiac disease. A total of 133 patients with celiac disease were tested for the HLA-DQA1 and HLA-DQB1 genes. Their corresponding allele and haplotype frequency distributions were estimated from the phenotypes found. The results were correlated with data from the clinical records. The DQ2 molecule was found in 93% of the patients, and DQ2 or DQ8 was found in 98%. The DQA1*0201-DQB1*0202 haplotype showed strong linkage disequilibrium. DQ2 homozygosis was significantly associated with female sex, earlier age at diagnosis, and shorter delay between onset of symptoms and diagnosis. Double-dose DQB1*02 (01-02) allele was more frequent in patients with the classic presentation of the disease. The genetic markers investigated may prove useful for diagnosing and managing celiac disease. With some clinical variables, correlations not previously described were found. These correlations have a moderate strength and, therefore, must be confirmed by other studies.


Performance of automated activity monitoring systems used in combination with timed artificial insemination compared to timed artificial insemination only in early lactation in dairy cows.
Identifying cows in estrus remains a challenge on dairy cattle farms, and tools and technologies have been developed and used to complement or replace visual detection of estrus. Automated activity monitoring (AAM) systems and timed artificial insemination (TAI) are technologies available to dairy farmers, but many factors can influence their relative performance. The objective of the present study was to compare reproductive performance of cows managed with an AAM system combined with TAI, or with a TAI program (Double Ovsynch) for insemination before 88 DIM. From April 2014 to April 2015, 998 cows from 2 herds were randomly assigned either to be inseminated at 85 ± 3 DIM exclusively using the Double Ovsynch protocol for TAI, or to be inseminated based on estrus detection by AAM without hormonal intervention between 50 and 75 DIM; if no alarm was detected by 75 DIM, cows were inseminated following the single Ovsynch protocol (AAM + Ovsynch). The herds used different AAM systems. Parity, hyperketonemia at wk 1 and 2 postpartum (PP), purulent vaginal discharge at wk 5 PP, body condition score at wk 7 PP, and anovulation to wk 9 PP were recorded. These health indicators did not significantly differ between treatments, but did between herds. The effect of treatment on pregnancy at first insemination and by 88 DIM were assessed using logistic regression models. Time to pregnancy was assessed using survival analysis. Results are reported from intention-to-treat analyses. Treatment did not affect pregnancy at first insemination or pregnancy by 88 DIM, but we found significant interactions between treatment and herd for both outcomes. In herd 2, marginal mean pregnancy at first AI was greater with Double Ovsynch (38%) than AAM + Ovsynch (31%), but no difference was observed in herd 1 (Double Ovsynch = 31%; AAM + Ovsynch = 34%). By 88 DIM, a smaller proportion of cows in herd 1 were pregnant in Double Ovsynch (31%) than AAM + Ovsynch (49%), but there was no difference in herd 2 (Double Ovsynch = 38%; AAM + Ovsynch = 38%). We observed a treatment by herd interaction for median (95% confidence interval) time to pregnancy, which were, in herd 1, 110 (106 to 129) and 98 (88 to 113) d, and, in herd 2, 126 (113 to 139) and 116 (105 to 131) d for the Double Ovsynch and AAM + Ovsynch treatments, respectively. The relative performance of AAM-based reproductive management compared with TAI only is likely influenced by herd-specific variables, in particular related to insemination rate when estrus detection is employed.


Hybrid plan verification for intensity-modulated radiation therapy (IMRT) using the 2D ionization chamber array I'mRT MatriXX--a feasibility study.
The 2D ionization chamber array I'mRT MatriXX (IBA, Schwarzenbruck, Germany) has been developed for absolute 2D dosimetry and verification of intensity-modulated radiation therapy (IMRT) for perpendicular beam incidence. The aim of this study is to evaluate the applicability of I'mRT MatriXX for oblique beam incidence and hybrid plan verification of IMRT with original gantry angles. For the assessment of angular dependence, open fields with gantry angles in steps of 10 degrees were calculated on a CT scan of I'mRT MatriXX. For hybrid plan verification, 17 clinical IMRT plans and one rotational plan were used. Calculations were performed with pencil beam (PB), collapsed cone (CC) and Monte Carlo (MC) methods, which had been previously validated. Measurements were conducted on an Elekta SynergyS linear accelerator. To assess the potential and limitations of the system, gamma evaluation was performed with different dose tolerances and distances to agreement. Hybrid plan verification passed the gamma test with 4% dose tolerance and 3 mm distance to agreement in all cases, in 82-88% of the cases for tolerances of 3%/3 mm, and in 59-76% of the cases if 3%/2 mm were used. Separate evaluation of the low dose and high dose regions showed that I'mRT MatriXX can be used for hybrid plan verification of IMRT plans within 3% dose tolerance and 3 mm distance to agreement with a relaxed dose tolerance of 4% in the low dose region outside the multileaf collimator (MLC).


A double-blind, randomized, controlled trial of topical polysporin triple compound versus topical mupirocin for the eradication of colonization with methicillin-resistant Staphylococcus aureus in a complex continuing care population.
Intranasal mupirocin or Polysporin Triple (PT) ointment (polymyxin B, bacitracin, gramicidin), in combination with chlorhexidine body washes, have been used for eradicating methicillin-resistant Staphylococcus aureus (MRSA), but no comparative studies have been done. A double-blind, randomized, controlled clinical trial to compare the efficacy of mupirocin versus PT ointment in combination with chlorhexidine body washes in eradicating MRSA carriage was conducted. Asymptomatic MRSA carriers, medically stable and at least 18 years of age who were patients on medical wards, received twice daily application of either mupirocin or PT ointment to the anterior nares plus once daily 2% chlorhexidine body washes for seven days. Follow-up swabs from multiple sites using broth enrichment were conducted at 48 h, and one, two, four, eight and 12 weeks. Of 103 patients eligible for analysis (54 mupirocin; 49 PT), no significant differences between the two groups with respect to baseline demographics, risk factors for MRSA or MRSA colonization sites were noted. At 48 h, 35 of 54 (65%) patients in the mupirocin group versus 15 of 49 (31%) in the PT group (P=0.001) were found to be MRSA negative at all sites. Significant differences were observed at one and two weeks but were not maintained at other intervals. In those with complete microbiological follow-up, MRSA eradication at all sites occurred in 12 of 39 (30.8%) mupirocin- and one of 36 (2.8%) PT-treated patients (P=0.001). Both agents demonstrated poor efficacy and PT was significantly less efficacious than mupirocin at 12 weeks in eradicating MRSA from all sites.


Characterization, bioactivity and ampicillin release kinetics of TiO2 and TiO24SiO2 synthesized by sol-gel processing.
Local drug delivery of antimicrobics by sustained release delivery system can be used to treat periodontal disease. Advantages of these systems may include maintaining high levels of antibiotic in the gingival crevicular fluid for a sustained period of time and ease of use with high patient acceptance. The materials used are TiO(2) and TiO(2)4SiO(2), mixed with sodium ampicillin, a broad-spectrum antibiotic, have been synthesized by sol-gel method. The amorphous nature of the gels was ascertained by X-ray diffraction analysis. Release kinetics in a simulated body fluid (SBF) have been subsequently investigated. The amount of sodium ampicillin released has been detected by UV-VIS spectroscopy and SEM. The release kinetics seems to occur in more than one stage. HPLC analysis has also been taken to ensure the integrity of ampicillin after the synthetic treatment. Finally, SEM micrographs and EDS analysis showed the formation of a hydroxyapatite layer on the surface of the samples soaked in SBF. Both the materials showed good release and could be used as drug delivery bioactive systems. High antimicrobial effects of samples against Escherichia coli and Streptococcus mutants were found.


Molecular cloning, DNA sequence analysis, and biochemical characterization of a novel 65-kDa FK506-binding protein (FKBP65).
We have identified a mouse gene encoding a 65-kDa protein (FKBP65) that shares homology with members of the FK506-binding protein (FKBP) class of immunophilins. Predicted amino acid sequence shows that this protein shares significant homology with FKBP12 (46%), FKBP13 (43%), FKBP25 (35%), and FKBP52 (26%). FKBP65 contains four predicted peptidylprolyl cistrans-isomerase (PPIase) signature domains, and, although similar in size, is distinct from FKBP52 (also identified as FKBP59, hsp56, or HBI), which contains three FKBP12-like PPIase domains. With N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as the substrate, recombinant FKBP65 is shown to accelerate the isomerization of the prolyl peptide bond with a catalytic efficiency similar to other family members. This isomerization activity is inhibited by FK506 and rapamycin, but is not sensitive to Cyclosporin A. Based on Northern blot analysis, FKBP65 mRNA transcripts are present in lung, spleen, heart, brain, and testis. A polyclonal antibody, raised against a COOH-terminal peptide (amino acid residues 566-581), was used to immunoprecipitate FKBP65 from NIH3T3 cells and demonstrate that FKBP65 is a glycoprotein. In addition, [32P]orthophosphate labeling experiments show that FKBP65 is also a phosphoprotein. These results suggest that FKBP65 is a new FKBP family member.


ortho-Cycloalkyl substituted N,N'-diaryliminoacenaphthene-Ni(ii) catalysts for polyethylene elastomers; exploring ring size and temperature effects.
A family of six unsymmetrical N,N'-diiminoacenaphthene-nickel(ii) bromide complexes, [1-{2,6-(Ph2CH)2-4-MeC6H2N}-2-(ArN)C2C10H6]NiBr2 (Ar = 2-(C6H11)-6-MeC6H2Ni1, 2-(C5H9)-6-MeC6H2Ni2, 2-(C8H15)-6-MeC6H2Ni3, 2-(C6H11)-4,6-Me2C6H2Ni4, 2-(C5H9)-4,6-Me2C6H2Ni5, 2-(C8H15)-4,6-Me2C6H2Ni6), each bearing one ring-size variable 4-R-2-methyl-6-cycloalkyl-substituted N-aryl group and one N'-4-methyl-2,6-dibenzhydrylphenyl group, have been prepared and fully characterized. The molecular structures of Ni1, Ni2, Ni3 and Ni5 reveal distorted tetrahedral geometries with different degrees of steric protection imparted by the two inequivalent N-aryl groups. On activation with either EASC or MMAO, all the precatalysts are highly active (up to 17.45 × 106 g PE mol-1 (Ni) h-1) for ethylene polymerization at 20-50 °C with their activities correlating with the type of cycloalkyl ortho-substituent: cyclooctyl (Ni6, Ni3) > the cyclopentyl (Ni5, Ni2) > cyclohexyl (Ni4, Ni1) for either R = H or Me. Moderately branched to hyperbranched polyethylenes (Tm's as low as 44.2 °C) can be obtained with molecular weights in the range 2.14-6.68 × 105 g mol-1 with the branching content enhanced by the temperature of the polymerization. Dynamic mechanical analysis (DMA) and monotonic tensile stress-strain tests have been employed on the polyethylene samples and reveal the more branched materials to show good elastic recovery properties (up to 75.5%).


Identification of functional regions of the Nun transcription termination protein of phage HK022 and the N antitermination protein of phage lambda using hybrid nun-N genes.
Phages lambda and HK022 express proteins N and Nun, respectively, each of which acts with a number of Escherichia coli host Nus factors at lambda NUT RNA sites, to influence transcription elongation. The lambda nut sites, nearly identical sequences located downstream of the early promoters, pL and pR, were first identified as cis-acting signals required for the action of N in forming termination-resistant transcription complexes. Surprisingly, the Nun protein, resembling N and expressed by another lambdoid phage, HK022, also acts with Nus proteins to terminate specifically transcription initiating at pL and pR near the lambda nut sites. Based on structural considerations of the amino acid sequences, we have constructed nine hybrid N-nun genes and used these hybrids to identify functional regions of the N and Nun proteins. Three classes of hybrid gene products were identified: (1) those that, like N, support antitermination, (2) those that, like Nun, terminate transcription, and (3) those that block N action but do not terminate transcription. We find that, similar to N, the amino-terminal portion of Nun is involved in RNA recognition. The more carboxy portions influence transcription elongation, antitermination (N) and termination (Nun). Depending on the derivations of the more carboxy regions, hybrids with either the N or Nun amino portions support either termination or antitermination. The activity of a hybrid protein may be influenced by the host strain depending on the nature of the rpoC locus, a locus encoding the beta' subunit of RNA polymerase. One of the hybrid proteins blocks antitermination when the rpoC locus is wild-type. The same hybrid in the presence of the rpoC100 mutation, which alters the beta' subunit, has antitermination activity. This result supports the argument that the beta' subunit plays an essential role in determining the progress of transcription elongation.


Impulsive rats are less maternal.
Early life environment and maternal care can have long-lasting effects on behavior and physiology. Previously, we found that compared to mother-reared (MR) female rats, rats reared without mothers, siblings, and nest, through artificially rearing (AR), show reduced levels of maternal behavior when they grow up. These effects can be reversed if AR pups are provided with extra "licking-like" tactile stimulation during the preweaning period [Gonzalez et al. [2001] Developmental Psychobiology, 38(1), 11-42]. We also found that AR rats are more action impulsive and have reduced attentional capacities in comparison to their MR siblings [Lovic, Fletcher, & Fleming, in preparation; Lovic & Fleming [2004] Behavioural Brain Research 148: 209-219]. However, it is unknown whether increased impulsivity contributes to reduced levels of maternal behaviors. The purpose of this study was to assess the relationship between impulsivity and maternal behavior in AR and MR rats. Female rats were reared with (MR) or without mothers (AR) and half of the AR rats received additional stroking stimulation. As adults, AR and MR rats were mated and maternal behavior towards their own pups was assessed. In addition, rats were assessed on impulsive action (differential reinforcement of low-rate schedule; DRL-20s). Consistent with previous findings, AR rats were both less maternal and more action impulsive than MR rats. Partial correlations revealed that impulsivity was inversely related to pup licking-impulsive rats were less maternal.


Decoupling initial electron beam parameters for Monte Carlo photon beam modelling by removing beam-modifying filters from the beam path.
A new method is presented to decouple the parameters of the incident e(-) beam hitting the target of the linear accelerator, which consists essentially in optimizing the agreement between measurements and calculations when the difference filter, which is an additional filter inserted in the linac head to obtain uniform lateral dose-profile curves for the high energy photon beam, and flattening filter are removed from the beam path. This leads to lateral dose-profile curves, which depend only on the mean energy of the incident electron beam, since the effect of the radial intensity distribution of the incident e- beam is negligible when both filters are absent. The location of the primary collimator and the thickness and density of the target are not considered as adjustable parameters, since a satisfactory working Monte Carlo model is obtained for the low energy photon beam (6 MV) of the linac using the same target and primary collimator. This method was applied to conclude that the mean energy of the incident e- beam for the high energy photon beam (18 MV) of our Elekta SLi Plus linac is equal to 14.9 MeV. After optimizing the mean energy, the modelling of the filters, in accordance with the information provided by the manufacturer, can be verified by positioning only one filter in the linac head while the other is removed. It is also demonstrated that the parameter setting for Bremsstrahlung angular sampling in BEAMnrc ('Simple' using the leading term of the Koch and Motz equation or 'KM' using the full equation) leads to different dose-profile curves for the same incident electron energy for the studied 18 MV beam. It is therefore important to perform the calculations in 'KM' mode. Note that both filters are not physically removed from the linac head. All filters remain present in the linac head and are only rotated out of the beam. This makes the described method applicable for practical usage since no recommissioning process is required.


Health disparities among Asian Americans and Pacific Islanders.
The Asian American and Pacific Islander (AAPI) group is the fastest-growing minority group in the United States. AAPIs have been touted in the literature as the "model minority" because of their achievements in the socioeconomic and educational spheres, which in certain categories are beyond the average levels of the dominant majority. However, generalizations such as these are very misleading, because they mask the glaring health disparities that are experienced by subgroups within the AAPI population. The purpose of this chapter is to explore the literature dealing with health disparities among AAPIs. Twenty-eight usable research reports were reviewed after a thorough review of the literature that spanned the years between 1990 and 2003. The review has revealed that the predominant psychosocial and cultural variables studied in research dealing with AAPI are acculturation, family and social networks, help-seeking behaviors, and cultural brokering. In general, research conducted on this group tended to be at the descriptive and comparative-correlational levels; more studies that investigate the effects of interventions to reduce or eliminate health disparities on this group are needed. The challenge is to build a body of knowledge on which to base future action.


Reference values for lung volumes in an Iranian population: introducing a new equation model.
Measurement of lung volumes, especially residual volume and total lung capacity are essential for assessment of restrictive lung disorders. Information regarding normative prediction values for lung volumes as measured by body plethysmography is scarce, and plethysmographic parameters are believed to be poorly reproducible. In this study, we report a comprehensive set of predictive equations for static lung volumes from a general population sample of urban Iranians as measured by body plethysmography. Standardized measurements were carried out on 1487 healthy nonsmoking volunteers (845 men and 642 women), aged six to 85 years, living in Isfahan, Iran. Nonlinear multiple regression analysis was used to calculate prediction equations based on subjects' ages and heights for the subdivisions of lung volumes [total lung capacity, functional residual capacity, residual volume, and residual volume/total lung capacity (%)], separately for the two genders. The derived equations were used to calculate prediction values for the subjects. The two sets of predicted and measured values were compared by paired sample t-test. Prediction equations based on a new nonlinear model, (alpha(1) x age + alpha(2) x age(n) + beta x height + c) which best fitted our data are presented. The measured and predicted values closely resemble and there is no significant difference between the two sets. Since increments in total lung capacity, functional residual capacity, and residual volume disclose air trapping within the lungs, their upper limits of normal are as important as the lower limits. So, we have presented both for the equations. Despite the usual beliefs we found rather reproducible prediction equations with high coefficient of determination (r2) and low standard error of estimate (SEE) in Iranian population.


Results of macular hole surgery combined with PEA and IOL.
We evaluated the factors affecting closure and postoperative visual acuity, as well as complications among idiopathic macular hole surgery cases comprising 631 eyes in 576 patients. Almost all the surgeries were combined with simultaneous intraocular lens surgery (triple surgery). In some cases, the standard method was accompanied by internal limiting membrane peeling around the macular hole or abrasion of retinal pigment epithelium at the base of the macular holes. We found that male gender and short eye axial length were associated with closure and postoperative visual acuity. Although the frequency of peripheral retinal tears during surgery was high, the frequency of postoperative retinal detachment was less than 2%. The reopening frequency was about 5% among all cases, and was highest among eyes that underwent the abrasion method. There were no other significant complications. Internal limiting membrane peeling is effective for treatment of cases with unfavorable preoperative conditions. However, the standard method is sufficiently effective for cases with favorable preoperative conditions. Further analysis is required to evaluate postoperative visual function by methods other than visual acuity. Further study of internal limiting membrane peeling, as a treatment alternative, is also required.


Is quadriceps H-reflex excitability a risk factor for patellofemoral pain?
Patellofemoral pain (PFP) is one of the most common conditions in orthopedic practice while recent evidence has suggested that it may be a predisposing factor to patellofemoral osteoarthritis. In addition to biomechanical alterations associated with the pathomechanisms underlying PFP, the investigation of neurophysiological alterations has provided novel information in the understanding of the pathophysiology of PFP. For instance, women with PFP present lower amplitude of the vastus medialis (VM) H-reflexes compared to pain-free controls, which suggests that the excitability of spinal reflexes might be a promising tool for discriminating woman with PFP in clinical practice. However, the cross-sectional design of the current research does not inform whether the reduced excitability predisposes to or is the consequence of PFP. Therefore, two hypotheses can be raised: (1) the reduction in excitability of the α-motoneurons is a risk factor for PFP; Or, (2) the reduction in H-reflex excitability is a consequence of PFP due to pain. If the former hypothesis is proven correct, it may help in the early identification of individuals with PFP. If the latter, it may help understand the reduced excitability as a consequence of the long-term pain, which may be interfering in the recovery of individuals with PFP in a long-term basis. In addition, exploring such hypotheses may have direct rehabilitative and prevention implications for PFP and its putative progression to knee osteoarthritis.


Isolation and characterization of a novel endogenous inhibitor of the proteasome.
A novel endogenous inhibitor of the proteasome (high molecular weight multicatalytic protease) has been isolated and characterized from human erythrocytes. After purification by ion-exchange and sizing chromatography, the inhibitor displayed a native molecular mass of approximately 200 kDa and contained a single subunit of 50 kDa with an isoelectric point of 6.9. Although the inhibitor noncompetitively blocks proteolysis of [methyl-14C]-alpha-casein (Ki = 7.1 x 10(-8) M) and inhibits hydrolysis of Suc-Leu-Leu-Val-Tyr-AMC, it did not affect hydrolysis of other peptide substrates, such as MeOSuc-Phe-Leu-Phe-MNA and Z-Ala-Arg-Arg-MNA. To further characterize the 50-kDa inhibitor, a monoclonal antibody (MI-8) was generated that showed specific binding upon Western blot analysis of both native PAGE and SDS-PAGE. Immunoprecipitation with MI-8 specifically removed inhibitor activity against the proteasome. The 50-kDa inhibitor is distinct from a previously described 40-kDa inhibitor of the proteasome (Murakami, K., & Etlinger, J.D. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 7588-7592) on the basis of lack of cross-reactivity with MI-8 and dissimilar peptide digest patterns. It is suggested that these endogenous inhibitors may have a role in ATP/ubiquitin-dependent proteolysis and/or other cellular functions involving this protease.


Antigen-specific immune reactions to ischemic stroke.
Brain proteins are detected in the cerebrospinal fluid (CSF) and blood of stroke patients and their concentration is related to the extent of brain damage. Antibodies against brain antigens develop after stroke, suggesting a humoral immune response to the brain injury. Furthermore, induced immune tolerance is beneficial in animal models of cerebral ischemia. The presence of circulating T cells sensitized against brain antigens, and antigen presenting cells (APCs) carrying brain antigens in draining lymphoid tissue of stroke patients support the notion that stroke might induce antigen-specific immune responses. After stroke, brain proteins that are normally hidden from the periphery, inflammatory mediators, and danger signals can exit the brain through several efflux routes. They can reach the blood after leaking out of the damaged blood-brain barrier (BBB) or following the drainage of interstitial fluid to the dural venous sinus, or reach the cervical lymph nodes through the nasal lymphatics following CSF drainage along the arachnoid sheaths of nerves across the nasal submucosa. The route and mode of access of brain antigens to lymphoid tissue could influence the type of response. Central and peripheral tolerance prevents autoimmunity, but the actual mechanisms of tolerance to brain antigens released into the periphery in the presence of inflammation, danger signals, and APCs, are not fully characterized. Stroke does not systematically trigger autoimmunity, but under certain circumstances, such as pronounced systemic inflammation or infection, autoreactive T cells could escape the tolerance controls. Further investigation is needed to elucidate whether antigen-specific immune events could underlie neurological complications impairing recovery from stroke.


Functional interactions within yeast mediator and evidence of differential subunit modifications.
It is possible to recruit RNA polymerase II to a target promoter and, thus, activate transcription by fusing Mediator subunits to a DNA binding domain. To investigate functional interactions within Mediator, we have tested such fusions of the lexA DNA binding domain to Med1, Med2, Gal11, Srb7, and Srb10 in wild type, med1, med2, gal11, sin4, srb8, srb10, and srb11 strains. We found that lexA-Med2 and lexA-Gal11 are strong activators that are independent of all Mediator subunits tested. lexA-Srb10 is a weak activator that depends on Srb8 and Srb11. lexA-Med1 and lexA-Srb7 are both cryptic activators that become active in the absence of Srb8, Srb10, Srb11, or Sin4. An unexpected finding was that lexA-VP16 differs from Gal4-VP16 in that it is independent of the activator binding Mediator module. Both lexA-Med1 and lexA-Srb7 are stably associated with Med4 and Med8, which suggests that they are incorporated into Mediator. Med4 and Med8 exist in two mobility forms that differ in their association with lexA-Med1 and lexA-Srb7. Within purified Mediator, Med4 is present as a phosphorylated lower mobility form. Taken together, these results suggest that assembly of Mediator is a multistep process that involves conversion of both Med4 and Med8 to their low mobility forms.


Percutaneous Pancreatic Stent Placement for Postoperative Pancreaticojejunostomy Stenosis: A Case Report.
Stenosis of the pancreatico-enteric anastomosis is one of the major complications of pancreaticoduodenectomy (PD). Endoscopic stent placement, has limited success rate as a nonsurgical treatment due to altered gastrointestinal anatomy. Percutaneous treatment is rarely attempted due to the technical difficulty in accessing the pancreatic duct. We reported a case of pancreaticojejunostomy stenosis after PD, in which a pancreatic stent was successfully placed using a rendezvous technique with a dual percutaneous approach.


A Chitinase from Aeromonas veronii CD3 with the potential to control myxozoan disease.
The class Myxosporea encompasses about 2,400 species, most of which are parasites of fish and cause serious damage in aquaculture. Due to the concerns about food safety issues and limited knowledge of Myxozoa life cycle and fish immune system, no chemicals, antibiotics or immune modulators are available to control myxozoa infection. Therefore, little can be done once Myxozoa establishment has occurred. In this paper we isolated Aeromonas veronii CD3 with significant myxospore shell valve-degrading ability from pond sediment. A 3,057-bp full-length chitinase gene was consequently cloned, and the corresponding mature, recombinant chitinase (ChiCD3) produced by Escherichia coli had substantial chitinase activity. The deduced sequence of ChiCD3 contained one catalytic domain, two chitin-binding domains, and one putative signal peptide. ChiCD3 had an optimal activity at 50°C and pH 6.0, and retained more than 50% of its optimal activity under warm water aquaculture conditions (∼30°C and pH ∼7.0). After incubation with ChiCD3, 38.0±4.8% of the myxospores had damaged shell valves, whereas myxospores incubated with commercially available chitinases remained intact. This study reveals a new strategy to control myxozoan disease. ChiCD3 that has capacity to damage the shell valve of myxospores can be supplemented into fish feed and used to control Myxozoa-induced diseases specifically.


Two distinct anti-allergic drugs, amlexanox and cromolyn, bind to the same kinds of calcium binding proteins, except calmodulin, in bovine lung extract.
In order to explore candidates for proteins required in exocytosis, we used two anti-allergic drugs, amlexanox and cromolyn, which inhibit IgE mediated degranulation of mast cells and basophils, as molecular probes in affinity chromatography. These two drugs chiefly bound to the same kinds of calcium binding proteins in bovine lung. These proteins were as follows: bovine calgranulin C homolog, an 8-kDa unknown protein, S-100L, calgranulin B, calcyphosine, and annexins I-V. The homologous affinity of the two drugs to these proteins is in accord with the similar anti-allergic property of both drugs. From these findings it is presumed that these drugs interact with these proteins and affect pharmacologically the degranulation.


Potentiation of the analgesic effects of tryptophan by allopurinol in rats.
The administration to rats of tryptophan (CAS 73-22-3) in high dosage causes a significant increase in pain threshold values. The analgesic effects of tryptophan are potentiated by allopurinol (CAS 315-30-0). The analgesic effects shown by tryptophan injection are associated with increased levels of serotonin and 5-hydroxyindoleacetic acid in some areas of the brain. The combined allopurinol and tryptophan treatment elevates the serotonin levels furtherly when they are compared with the values observed in animals receiving tryptophan only. The analgesia caused by tryptophan administration has been attributed to an increased activity of the serotoninergic system involved in the control of pain transmission.


Incomplete resection rate of cold snare polypectomy: a prospective single-arm observational study.
Background and study aims Cold snare polypectomy (CSP) is considered to be safe for the removal of subcentimeter colorectal polyps. This study aimed to determine the rate of incomplete CSP resection for subcentimeter neoplastic polyps at our center. Patients and methods Patients with small or diminutive adenomas (diameter 1 - 9 mm) were recruited to undergo CSP until no polyp was visible. After CSP, a 1 - 3 mm margin around the resection site was removed using endoscopic mucosal resection. The polyps and resection site marginal specimens were microscopically evaluated. Incomplete resection was defined as the presence of neoplastic tissue in the marginal specimen. We also calculated the frequency at which the polyp lateral margins could be assessed for completeness of resection. Results A total of 307 subcentimeter neoplastic polyps were removed from 120 patients. The incomplete resection rate was 3.9 % (95 % confidence interval [CI] 1.7 % - 6.1 %); incomplete resection was not associated with polyp size, location, morphology, or operator experience. The polyp lateral margins could not be assessed adequately for 206 polyps (67.1 %). Interobserver agreement between incomplete resection and lateral polyp margins that were inadequate for assessment was poor (κ = 0.029, 95 %CI 0 - 0.04). Female sex was an independent risk factor for incomplete resection (odds ratio 4.41, 95 %CI 1.26 - 15.48; P = 0.02). Conclusions At our center, CSP resection was associated with a moderate rate of incomplete resection, which was not associated with polyp characteristics. However, adequate evaluation of resection may not be routinely possible using the lateral margin from subcentimeter polyps that were removed using CSP.Trial registered at University Hospital Medical Information Network (UMIN 000010879).


Cholinergic stimulation with pyridostigmine reduces the QTc interval in coronary artery disease.
Parasympathetic dysfunction is an independent risk factor in patients with coronary artery disease; thus, cholinergic stimulation is a potential therapeutic measure that may be protective by acting on ventricular repolarization. The purpose of the present study was to determine the effects of pyridostigmine bromide (PYR), a reversible anticholinesterase agent, on the electrocardiographic variables, particularly QTc interval, in patients with stable coronary artery disease. In a randomized double-blind crossover placebo-controlled study, simultaneous 12-lead electrocardiographic tracings were obtained at rest from 10 patients with exercise-induced myocardial ischemia before and 2 h after the oral administration of 45 mg PYR or placebo. PYR increased the RR intervals (pre: 921 +/- 27 ms vs post: 1127 +/- 37 ms; P<0.01) and, in contrast with placebo, decreased the QTc interval (pre: 401 +/- 3 ms vs post: 382 +/- 3 ms; P<0.01). No other electrocardiographic variables were modified (PR segment, QT interval, QT and QTc dispersions). Cholinergic stimulation with PYR caused bradycardia and reduced the QTc interval without important side effects in patients with coronary disease. These effects, if confirmed in studies over longer periods of administration, may suggest a cardioprotection by cholinergic stimulation with PYR.


Isolation and characterization of a reovirus from common eiders (Somateria mollissima) from Finland.
Samples of brain, intestine, liver, lung, spleen, and bursa of Fabricius were collected from five common eider (Somateria mollissima) duckling carcasses during a die-off in the western Gulf of Finland (59 degrees 50'N, 23 degrees 15'E) in June 1996. No viral activity was observed in specific-pathogen-free chicken embryos inoculated with tissue suspensions, but samples of bursa of Fabricius from three birds were positive when inoculated into Muscovy duck (Cairina moschata) embryo fibroblasts. The isolates were characterized as nonenveloped RNA viruses and possessed several characteristics of the genus Orthoreovirus. Virus particles were icosahedral with a mean diameter of 72 nm and were stable at pH 3.0; their genome was separated into 10 segments by polyacrylamide gel electrophoresis. Mallard (Anas platyrhynchos) ducklings experimentally infected with the eider reovirus showed elevated serum activities of aspartate aminotransferase, creatine kinase, and lactate dehydrogenase enzymes and focal hemorrhages in the liver, spleen, and bursa of Fabricius. During 1997-99, the prevalence of neutralizing antibodies to the isolated virus ranged from 0 to 86% in 302 serum samples collected from incubating eider hens at three nesting areas along coastal Finland. The highest seroprevalence was found in Hanko in 1999, just weeks before reports of an uninvestigated mortality event resulting in the death of an estimated 98% of ducklings at that location. These findings raise the question of potential involvement of the virus in poor duckling survival and eider population declines observed in several breeding areas along coastal Finland since the mid-1980s.


Improved measurement of B+ --> rho+ rho0 and determination of the quark-mixing phase angle alpha.
We present improved measurements of the branching fraction B, the longitudinal polarization fraction f{L}, and the direct CP asymmetry A{CP} in the B meson decay channel B;{+}-->rho;{+}rho;{0}. The data sample was collected with the BABAR detector at SLAC. The results are B(B;{+}-->rho;{+}rho;{0})=(23.7+/-1.4+/-1.4) x 10;{-6}, f{L}=0.950+/-0.015+/-0.006, and A{CP}=-0.054+/-0.055+/-0.010, where the uncertainties are statistical and systematic, respectively. Based on these results, we perform an isospin analysis and determine the Cabibbo-Kobayashi-Maskawa phase angle alpha=arg(-V{td}V{tb};/V{ud}V{ub}) to be (92.4{-6.5};{+6.0}) degrees.


The role of thermal history on spontaneous polarization and phase transitions of amorphous solid water films studied by contact potential difference measurements.
Monitoring thermal processes occurring in molecular films on surfaces can provide insights into physical events such as morphology changes and phase transitions. Here, we demonstrate that temperature-programmed contact potential difference (TP-∆CPD) measurements employed by a Kelvin probe under ultrahigh vacuum conditions and their temperature derivative can track films' restructure and crystallization occurring in amorphous solid water (ASW) at temperatures well below the onset of film desorption. The effects of growth temperature and films' thickness on the spontaneous polarization that develops within ASW films grown at 33 K-120 K on top of a Ru(0001) substrate are reported. Electric fields of ∼106 V/m are developed within the ASW films despite low average levels of molecular dipole alignment (<0.01%) normal to the substrate plane. Upon annealing, an irreversible morphology-dependent depolarization has been recorded, indicating that the ASW films keep a "memory" of their thermal history. We demonstrate that TP-∆CPD measurements can track the collapse of the porous structure at temperatures above the growth and the ASW-ice Ic and ASW-ice Ih transitions at 131 K and 157 K, respectively. These observations have interesting implications for physical and chemical processes that take place at the interstellar medium such as planetary formation and photon- and electron-induced synthesis of new molecules.


[A study on the newly designed platysma myocutaneous flap and its clinical applications].
From 1978 to 1991, the platysma myocutaneous flap of different designs was used to treat 69 patients with tumor extirpation defects of temporomandibular ankylosis. The conventional platysma myocutaneous flap was used to repair buccal defects. The combined platysma and sternocleidomastoid myocutaneous flap was used to reconstruct the tongue and the floor of the mouth. The innovated platysma myocutaneous flap, i.e. folded platysma myocutaneous flap was used to reconstruct the temporomandibular joint capsule for true ankylosis. All the procedure was completed in one stage and the operative results were satisfactory.


Suicide risk assessment: time to think again?
This paper considers recent research on suicide risk assessment to support calls for a 'rethink' of our assessment of the patients in our care, along with the adoption of a more collaborative approach to care planning with service users who remain at risk of self-harm and in need of a plan for their safety.


Sternal transplant using cadaveric allograft: quantitative and qualitative assessment of bone healing by computed tomography.
Sternal transplant using cadaveric allograft (STCA) is a complex and rarely performed surgical procedure usually applied for massive bone tissue loss, sternotomy complications, or neoplastic resections. Although radiological imaging and especially computed tomography (CT) is routinely applied for the post-surgical assessment, up to now, a standardized approach evaluating the outcome of STCAs is missing. Therefore, aim of this study was to qualitatively and quantitatively evaluate, by CT, bone healing after STCA. The first and the last available postsurgical CT of patients who underwent STCA in two tertiary centers between 2009 and 2017 were collected. Standardized regions of interest were applied on the cancellous bone along the transplanted sternum, and, as reference, on the fourth thoracic vertebra, at both time points, collecting the density values. The areas nearby the fixation devices were assessed by a four-points qualitative score. To evaluate the mineralization, the analysis of the variance (ANOVA) with post-hoc Bonferroni correction was applied for the quantitative measurements while the Wilcoxon test was used for the qualitative score (P<0.05). To evaluate the intra-rater reliability of the qualitative and the quantitative analyses, the same rater repeated the measurements after two months and the Cohen's kappa (k) and the intraclass correlation coefficient (ICC) were computed. Fourteen patients (11 females, 61±12.8 years) were examined. The first control CTs were performed 32±40.26 days after the STCA and the last CT were acquired after 729±745 days. The quantitative and the qualitative score significantly increased between the two intervals (P<0.05, each). The density of the transplanted sternum was lower than that of the vertebral reference at the first CT (P=0.006) while no differences occurred at the last control (P=0.361). The assessments showed high intra-rater reliability and agreement (ICC ≥0.890, k≥0.906). The hereby-proposed qualitative and quantitative methods demonstrated to be good tools for assessing bone healing after STCA.


Early and Late Atrial Arrhythmias After Lung Transplantation - Incidence, Predictive Factors and Impact on Mortality.
Atrial arrhythmias (AAs) are frequent after lung transplantation (LT) and late postoperatively. Several predictive factors of early postoperative AAs after LT have been identified but those of late AAs remain unknown. Whether AA after LT affects mortality is still being debated. This study assessed in a large cohort of LT patients the incidence of AAs early and late after surgery, their predictive factors and their effect on mortality.Methods and Results:We studied 271 consecutive LT patients over 9 years. Mean follow-up was 2.9±2.4 years. 33% patients developed postoperative AAs. Age (odds ratio (OR) 2.35; confidence interval (CI) [1.31-4.24]; P=0.004) and chronic obstructive pulmonary disease (OR 2.13; CI [1.12-4.03]; P=0.02) were independent predictive factors of early AAs. Late AAs occurred 2.2±2.7 years after transplant in 8.8% of the patients. Pretransplant systolic pulmonary arterial pressure (PTsPAP) was the only independent predictive factor of late AA (OR 1.028; CI [1.001-1.056]; P=0.04). Double LT was associated with long-term freedom from atrial fibrillation (AF) but not from atrial flutter (AFL). Early and late AAs after surgery had no effect on mortality. Double LT was associated with better survival. Early AA following LT is common in contrast with the low occurrence of late, often organized, AA. Early and late AAs do not affect mortality. PTsPAP is an independent predictor of late AA. Double LT protects against late AF but not AFL.


NF-kappaB regulates the expression of Nucling, a novel apoptosis regulator, with involvement of proteasome and caspase for its degradation.
Nucling is identified as a novel regulator of apoptosis. In this study, we investigated the nuclear factor-κB (NF-κB)-dependent mechanism of Nucling expression, as well as the degradation pathways mediated by proteasome system and caspase activation. Using chromatin immunoprecipitation assay in wild-type mouse embryonic fibroblasts (WT MEFs), we found that NF-κB p65 could bind to the κB motifs in the promoter regions of Nucling gene at four putative-binding sites. By real-time PCR and immunoblot, we confirmed that Nucling expression was up-regulated by tumour necrosis factor-α (TNF-α) stimulation in WT MEFs, but not in NF-κB p50 knockout MEFs. On the other hand, we investigated the degradation of Nucling in connection with proteasome and caspase by using cycloheximide chase. The results showed that Nucling is a short-lived protein, and its degradation was recovered by proteasome inhibitor MG132. Moreover, under TNF-α stimulation, degradation of Nucling was recovered by pan-caspase inhibitor zVAD-fmk. Taken together, we propose a mechanism of Nucling intracellular metabolism. Nucling expression is induced by canonical NF-κB signalling pathway, whereas Nucling is undergoing proteasome degradation, as well as being cleaved by caspase system under stress conditions. This opens a new perspective for studying the NF-κB dependent regulation mechanism of cell death and survival.


Recent Advances in Stimuli-Responsive DNA-Based Hydrogels.
Stimuli-responsive DNA-based hydrogels are attracting growing interest because of their smart responsiveness, excellent biocompatibility, regulated biodegradability, and programmable design properties. Integration of reconfigurable DNA architectures and switchable supramolecular moieties (as cross-linkers) in hydrogels by responding to external stimuli provides an ideal approach for the reversible tuning structural and mechanical properties of the hydrogels, which can be exploited in the development of intelligent DNA-based materials. This review highlights recent advances in the design of responsive pure DNA hydrogels, DNA-polymer hybrid hydrogels, and autonomous DNA-based hydrogels with transient behaviors. A variety of chemically and physically triggered DNA-based stimuli-responsive hydrogels and their versatile applications in biosensing, biocatalysis, cell culture and separation, drug delivery, shape memory, self-healing, and robotic actuators are summarized. Finally, we address the key challenges that the field will face in the coming years, and future prospects are identified.


Suppression of phase separation in LiFePO₄ nanoparticles during battery discharge.
Using a novel electrochemical phase-field model, we question the common belief that Li(X)FePO(4) nanoparticles always separate into Li-rich and Li-poor phases during battery discharge. For small currents, spinodal decomposition or nucleation leads to moving phase boundaries. Above a critical current density (in the Tafel regime), the spinodal disappears, and particles fill homogeneously, which may explain the superior rate capability and long cycle life of nano-LiFePO(4) cathodes.


[Medico-economic assessment of two methods for implementing thyroid testing guidelines].
To compare independent and combined effectiveness and cost-effectiveness of two implementation interventions of guidelines for ordering thyroid function tests. The two implementation interventions were a Memorandum Pocket Card (MPC) and a Test Request Form (TRF). Intervention groups were wards. The study used an experimental 2*2 factorial design with matching hospitals according to size and activity and wards according to pre-intervention appropriateness for test ordering. Four ward groups were established: the dual intervention group, the order form group, the pocket card group and the control group. Physicians in all groups received guidelines and were invited to a local information meeting. The main outcome measure of effectiveness was the Guideline Conformity Rate (GCR). The cost-effectiveness ratio was the cost difference between the tested intervention and the control intervention upon effectiveness difference between the tested intervention and the control intervention. Six hospitals participated in the study (two middle-sized hospitals, two small-sized hospitals and two psychiatric hospitals). A total of 1412 orders for thyroid function tests were collected. GCR was 78% in the dual intervention group, 83% in the order form group, 73% in the pocket card group and 62% in the control group. The interaction between TRF and MPC was not significant (B=-0.70, p=0.21). Compared to simple information, TRF was effective in increasing GCR (OR=2.65, 95% Confidence Interval [CI]: 1.52-4.62), unlike MPC (OR=1.28, CI: 0.75-2.19). TRF was the less expensive and the most effective intervention. Using a robust design, our study shows a greater effectiveness of TRF than MPC and their association in implementing thyroid function test guidelines. The development of clinical practice improvement projects through the second procedure of accreditation in France is a good opportunity to develop a guidelines implementation research project.


Probing triplex formation by EPR spectroscopy using a newly synthesized spin label for oligonucleotides.
Spin labels have been extensively used to study the dynamics of oligonucleotides. Spin labels that are more rigidly attached to a base in an oligonucleotide experience much larger changes in their range of motion than those that are loosely tethered. Thus, their electron paramagnetic resonance spectra show larger changes in response to differences in the mobility of the oligonucleotides to which they are attached. An example of this is 5-(2,2,5,5-tetramethyl-3-ethynylpyrrolidine-1-oxyl)-uridine (1). How ever, the synthesis of this modified DNA base is quite involved and, here, we report the synthesis of a new spin-labeled DNA base, 5-(2,2,6,6-tetramethyl-4-ethynylpiperidyl-3-ene-1-oxyl)-uridine (2). This spin label is readily prepared in half the number of steps required for 1, and yet behaves in a spectroscopically analogous manner to 1 in oligonucleotides. Finally, it is shown here that both spin labels 1 and 2 can be used to detect the formation of both double-stranded and triplex DNA.


Sexual desire during the menopausal transition and early postmenopause: observations from the Seattle Midlife Women's Health Study.
To describe levels of sexual desire across the menopausal transition (MT) and early postmenopause (PM), including effects of age, MT-related factors, health, stress, symptoms (hot flash, sleep, mood), and social opportunity factors. A subset of Seattle Midlife Women's Health Study (SMWHS) participants who provided data during the early reproductive, early and late menopausal transition stages, or postmenopause (n = 286), including menstrual calendars for staging the MT, annual health reports between 1990 and 2005, and morning urine samples assayed for estrone glucuronide (E(1)G), testosterone (T), and follicle-stimulating hormone (FSH) was included. Multilevel modeling using the R program was used to test factors related to sexual desire. Women experienced a significant decrease in sexual desire during the late MT stage (p < 0.01) and early PM (p < 0.0001). Those with higher urinary E(1)G and T reported significantly higher levels of sexual desire, whereas those with higher FSH levels reported significantly lower sexual desire (p < 0.0001, 0.06, and 0.0002, respectively). Women using hormone therapy also reported higher sexual desire (p = 0.02). Those reporting higher perceived stress reported lower sexual desire (p < 0.0001), but history of sexual abuse did not have a significant effect. Those most troubled by symptoms of hot flashes, fatigue, depressed mood, anxiety, difficulty getting to sleep, early morning awakening, and awakening during the night also reported significantly lower sexual desire (p range from <0.03 to 0.0001), but there was no effect of vaginal dryness. Women with better perceived health reported higher sexual desire (p < 0.0001), and those reporting more exercise and more alcohol intake also reported greater sexual desire (p < 0.0001). Having a partner was associated with lower sexual desire. Clinicians working with women traversing the MT should be aware that promoting healthy sexual functioning among midlife women requires consideration of their changing biology as well as ongoing life challenges.


Predictors of Track Test Performance in Drivers with Stroke.
To identify in-house assessment criteria to predict outcomes of driving tests in patients with stroke who wish to resume driving. A total of 181 patients with stroke who attended Fukui General Hospital (as outpatients or inpatients) between 2003 and 2015 and who had no obvious motor impairment were included in the study. All subjects underwent a neuropsychological examination, a driving simulator test, and a track test at a driving school. Based on their performance in the track test, the subjects were divided into capable drivers (CD group) and incapable drivers (ID group). Intergroup differences in test results were evaluated. Logistic regression analysis was performed using age and outcomes of Trail-Making Tests A and B, and Symbol Digit Modalities Test (SDMT) as independent variables and track test performance as the dependent variable. The ID group performed worse than the CD group in most aspects of the neuropsychological examination. There was no significant difference between the two groups with respect to any component of the driving simulator test. SDMT values were extracted from the logistic regression analysis, with an Odds Ratio of 1.05 (p=0.028). On receiver operating characteristic curve analysis (with the area under the curve of 0.76), at the SDMT achievement rate < 37.3%, there was a sensitivity of 65% and specificity of 79% for the identification of driving inability. Neuropsychological tests are useful for evaluating the ability of patients with stroke to resume driving. In particular, SDMT is the most suitable test for predicting driving test outcomes.


Neurotoxicity following the Ingestion of Bilimbi Fruit (Averrhoa bilimbi) in an End-Stage Renal Disease Patient on Hemodialysis.
The toxic effects of the ingestion of star fruit (Averrhoa carambola) in chronic kidney disease patients are well described in the literature. Recently, the compound caramboxin has been isolated, explaining the mechanisms of its neurotoxicity. Bilimbi fruit belongs to the family Oxalidaceae, Averrhoa bilimbi species, and exhibits similar biochemical characteristics to star fruit. To report the case of a patient with chronic kidney disease who developed a seizure disorder after the ingestion of bilimbi fruit. A 69-year-old man with chronic kidney disease on hemodialysis therapy had intractable hiccups, myoclonus, and generalized tonic-clonic seizures after the consumption of a moderate amount of bilimbi fruit. The electroencephalogram showed a pattern of seizure disorder despite the use of anticonvulsant drugs. Renal replacement therapy was maintained during the whole period and prescribed according to the patient's hemodynamic status. Despite showing clinical resolution of the seizure disorder, the patient died on the 27th day of hospitalization for infectious complications. The neurologic status without any other known cause and with clear temporal association with the ingestion of the fruit suggests the diagnosis of neurotoxicity. We propose the hypothesis that the bilimbi fruit has neurotoxic effects similar to those exhibited by the star fruit.


Nutrition and the healthy adult.
Great public concern over the constituents of diets, encouraged by widely publicised and often conflicting advice on what constitutes 'healthy' and 'unhealthy' items, is placing pressures on nurses to understand the nutritional make-up of foods and their uses and abuses. Anne Halliday takes a general look at the requirements of the healthy adult and suggests that there is a need for individuals to review the nature of their whole diet, not merely one or two constituents of it. Nurses will find her article invaluable from a personal as well as professional perspective.


Process Mapping to inform implementation of Trauma-Informed Care for youth aged 14-24 with HIV in the Southern United States.
Trauma-Informed Care (TIC) is an evidence-based approach for improving health outcomes by providing systematic, trauma- sensitive and -responsive care. Because TIC adoption varies by setting and population, Implementation Science (IS) is particularly well-suited to guide roll-out efforts. Process Mapping (PM) is an IS model for creating shared visual depictions of systems as they are to identify rate-limiting steps of intervention adoption, but guidance on how to apply PM to guide TIC adoption is lacking. Authors of this study aimed to develop a novel method for conducting TIC-focused PM. A real-life TIC implementation study is presented to show how TIC-focused PM was conducted in the case example of a pediatric HIV clinic in a Southern urban area with a high burden of psychological trauma among youth with HIV. A five-phase PM model was applied to evince clinic standards of care, including Preparation, planning and process identification; Data and information gathering; Map generation; Analysis; and Taking it forward. Practices and conditions from four TIC domains were assessed, including Trauma responsive services; Practices of inclusivity, safety, and wellness; Training and sustaining trauma responsiveness; and Cultural responsiveness. The TIC-focused PM method indicated the case clinic provided limited and non-systematic patient trauma screening, assessment, and interventions; limited efforts to promote professional quality of life and elicit and integrate patient experiences and preferences for care; no ongoing efforts to train and prepare workforce for trauma- sensitive or -responsive care; and no clinic-specific efforts to promote diversity, equity, and inclusion for patients and personnel. Principles and constructs of resilience-focused TIC were synthesized with a five-phase PM model to generate a baseline depiction of TIC in a pediatric HIV clinic. Results will inform the implementation of TIC in the clinic. Future champions may follow the TIC-focused PM model to guide context-tailored TIC adoption.


A quality assurance programme.
Some critics consider quality assurance (QA) programmes and medical audit inappropriate for India's diverse hospitals; others feel that they are vital tools for the optimisation of scarce resources. The Indian Hospital Association successfully initiated a QA programme for its teaching hospitals, the preparation and results of which are described here along with the reproduction of the questionnaire used.


[Determination of the arterial input function in mouse-models using clinical MRI].
Dynamic contrast enhanced Magnetic Resonance Imaging is a promising method for quantitative analysis of tumor perfusion and is increasingly used in study of cancer in small animal models. In those studies the determination of the arterial input function (AIF) of the target tissue can be the first step. Series of short-axis images of the heart were acquired during administration of a bolus of Gd-DTPA using saturation-recovery gradient echo pulse sequences. The AIF was determined from the changes of the signal intensity in the left ventricle. The native T1 relaxation times and AIF were determined for 11 mice. An average value of (1.16+/-0.09) s for the native T1 relaxation time was measured. However, the AIF showed significant inter animal variability, as previously observed by other authors. The inter-animal variability shows, that a direct measurement of the AIF is reasonable to avoid significant errors. The proposed method for determination of the AIF proved to be reliable.


Capillary condensation as a morphological transition.
The process of capillary condensation/evaporation in cylindrical pores is considered within the idea of symmetry breaking. Capillary condensation/evaporation is treated as a morphological transition between the wetting film configurations of different symmetry. We considered two models: (i) the classical Laplace theory of capillarity and (ii) the Derjaguin model which takes into account the surface forces expressed in terms of the disjoining pressure. Following the idea of Everett and Haynes, the problem of condensation/evaporation is considered as a transition from bumps/undulations to lenses. Using the method of phase portraits, we discuss the mathematical mechanisms of this transition hidden in the Laplace and Derjaguin equations. Analyzing the energetic barriers of the bump and lens formation, it is shown that the bump formation is a prerogative of capillary condensation: for the vapor-liquid transition in a pore, the bump plays the same role as the spherical nucleus in a bulk fluid. We show also that the Derjaguin model admits a variety of interfacial configurations responsible for film patterning at specific conditions.


[Effect of Observation Window at Peripheral Intravenous Catheter Site on Early Recognition of Infiltration among Hospitalized Children].
The aim of this study was to identify the effect of an observation window (OW) at peripheral intravenous (IV) catheter sites on early detection of IV infiltration among hospitalized children. This was a retrospective observational study with history control group design. Participants were children who had IV infiltration after peripheral catheterization when hospitalized from January to May, 2014 and January to May, 2015 at a children's hospital located in Yangsan city, Korea. The 193 patients, who were hospitalized from January to May, 2014 formed the control group and did not have OW, and the 167 patients, who were hospitalized from January to May, 2015 formed the window group and had OW. Data were analyzed using χ²-test, independent samples t-test and multiple logistic regression. First stage IV infiltration was 39.5% for the window group and 25.9% for the control group, which was significantly different (p=.007). The likelihood of 2nd stage and above IV infiltration decreased by 44% in the window group, which was significantly different (p=.014). OW at the peripheral IV catheter site was found to be an effective measure in early recognition of IV infiltration. Considering the effect of OW, we recommend that nurses should make an OW with transparent dressing during stabilization of the IV catheter site in hospitalized children in clinical settings.


In vivo effects of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF), alone and associated with zidovudine, on HIV-1 replication.
The effects of the administration of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) on HIV-1 replication were evaluated in 15 patients with advanced HIV-1 disease and severe leukopenia, by monitoring immunocomplex dissociated p24 antigenemia, during 21 overall courses of therapy with rHuGM-CSF (lasting 2 to 27 weeks), alone or associated with zidovudine. During most treatment courses with rHuGM-CSF (17 out of 21), no significant modifications of HIV-1 antigenemia were recognized. A remarkable increase in viral replication occurred in only two courses out of 13 performed with rHuGM-CSF alone, while a significant reduction of antigenemia was observed in two courses of rHuGM-CSF out of 8 administered with zidovudine, after 10 weeks of combined treatment. Our experience is discussed on the grounds of both experimental and clinical investigations dealing with interactions between rHuGM-CSF and zidovudine during HIV-1 disease, focusing on risks of increased viral burden during treatment with rHuGM-CSF alone, and the synergistic activity of the combination with zidovudine against HIV-1 replication.


Production of a suppressor factor by human adherent cells treated with Mycobacterium tuberculosis: absence in systemic lupus erythematosus.
When human peripheral blood mononuclear cells are activated by mitogens in the presence of Mycobacterium tuberculosis (M. tuberculosis), considerable suppression of 3H-thymidine incorporation is observed. Proliferation of mononuclear cells from patients with SLE was not suppressed by treatment with mycobacteria. Analysis of suppressor effect indicated that normal peripheral blood adherent cells treated with mycobacteria release a soluble factor which activates a precursor cell population to become active suppressor T cells. Although lymphocytes from patients with SLE were responsive to suppressor factor produced by normal adherent cells treated with mycobacteria, SLE adherent cells were incapable of producing suppressor factor when treated in the same way. In order to determine whether the inability of SLE adherent cells to produce suppressor factor was due to the presence of immune complexes on the surface of these cells, SLE adherent cells were trypsinized or preincubated prior to treatment with mycobacteria. Neither of these manoeuvres restored the ability of SLE adherent cells to produce suppressor factor. Furthermore, normal adherent cells continued to produce the factor after prior treatment with varying concentrations of human serum albumin-anti-human serum albumin complexes. The results suggest that a basic adherent cell defect exists in SLE and that under certain circumstances this may give rise to a secondary defect of suppressor cell activation.


Crystal packing of the c(6)-type cytochrome OmcF from Geobacter sulfurreducens is mediated by an N-terminal Strep-tag II.
The putative outer membrane c-type cytochrome OmcF from Geobacter sulfurreducens contains a single haem group and shows homology to soluble cytochromes c(6), a class of electron-transfer proteins that are typically found in cyanobacterial photosynthetic electron-transfer chains. OmcF was overexpressed heterologously in Escherichia coli as an N-terminal Strep-tag II fusion protein and isolated using streptactin-affinity chromatography followed by size-exclusion chromatography. The structure was solved by Fe SAD using data collected to a resolution of 1.86 A on a rotating copper-anode X-ray generator. In the crystal, packing interactions in one dimension were exclusively mediated through the Strep-tag II sequence. The tag and linker regions were in contact with three further monomers of OmcF, leading to a well defined electron-density map for this engineered and secondary-structure-free region of the molecule.


Physicians value patient review of their electronic health record data as a means to improve accuracy of medication list documentation.
Providers place great value on their patients as sources of clinical information. Patient access to and review of their medication list from their electronic health record prior to a visit may improve the accuracy of medication documentation.


Enhancement of angiotensin-converting enzyme activity in the inner cortex of rat kidney by captopril.
The rat kidney was separated into the outer cortex, inner cortex, outer medulla and inner medulla or papilla, and the distribution of angiotensin-converting enzyme (ACE) in response to consecutive administrations of captopril was studied. In normal animals, the ACE activity in the inner cortex and outer medulla was about 10 and 3 times higher than in the outer cortex, respectively, and the activity in the inner medulla was much the same as that in the outer cortex. Captopril was given in doses of 30 and 100 mg/kg/day for 7 days, and the renal ACE activity on the 8th day was examined. Since it was assumed that the ACE activity might be lower than the full activity when the tissue contained captopril, diamide, a sulfhydryl oxidant, was used to eliminate the effect of any captopril remaining in the tissue extracts. However, this compound at concentrations over 1 mM enhanced the activity of ACE itself to about twice the value when assayed without diamide. Thus, oxidation with sufficient concentrations of diamide resulted in an enhancement of a maximal activity of ACE. When all samples were pretreated with 10 mM diamide and the ACE activity determined, captopril caused a dose-related increase in the ACE activity, but only in the inner cortex. We conclude that ACE locates predominantly in the inner cortex of the rat kidney and it is this area which has an altered ACE activity in response to captopril.


Acute Truncal Lymphedema Secondary to Axillary Metastatic Melanoma Presenting Like Cellulitis.
There are reported cases of diphencyprone used in treating cutaneous metastases of melanoma. Here, we report a patient with previous primary melanoma on his left back treated with surgical excision and lymphadenectomy, followed by radiotherapy for the recurrent tumor on the primary site. Despite radiotherapy and treatment with dabrafenib and trametinib, in-transit metastases have developed and topical diphencyprone was applied to these metastases. Six weeks later, the patient developed fever and a spreading erythematous tender indurated plaque covering the left side of the body including axillae, back, and flank, clinically suggestive of cellulitis. Systemic antibiotic therapy did not improve the condition and a biopsy showed sparse lymphocytic infiltrate. With the diagnosis of possible acute lymphedema, a CT scan was requested that showed significant axillary lymph node metastasis. The fever was considered secondary to dabrafenib and trametinib therapy. This case highlights that, in patients with lymphadenectomy, atypical forms of lymphedema on the body may appear. Truncal lymphedema is an infrequent event.


Factors associated with cortisol levels and health in 5-6-year-old children.
This study assesses the relationships between social context (family and inter-peer context), stress, and illness in 5-6-year-old children. To this end, data were collected on spontaneous social interpeer behavior; families provided data on stress, anxiety, and parental acceptance-rejection; and the children's pediatricians provided data relative to their health. Data on stress-related hormones (cortisol) were collected using saliva samples. The results revealed that none of the variables examined were significantly related to illness development in the subjects in the sample group. Cortisol levels, however, were positively associated with a record of chronic or congenital illnesses, the manifestation of behaviors related to the search for leadership status in the group and the presence of stressful events in the family environment. Despite finding no relationship between children's level of adrenocortical activity and the contracting or contingent development of diseases, we did find that chronic/congenital diseases may constitute a source of early stress in childhood. Certain conditions of uncertainty in the social context (family and interpeer) also seem to constitute different sources of stress.


The effect of the static magnetic field on the response of radiation survey instruments.
The effects on the response of eight radiation survey instruments in static magnetic fields up to 0.03 T (300 G) have been investigated. The instruments studied are the Xetex 303B Pacer, the Bicron Micro Rem survey meter, the Victoreen 450p survey meter, the Victoreen 440 survey meter, the SLAC orange meter, the Keithley 36150 survey meter, the Anderson-Braun neutron remmeter, and the Victoreen 488 neutron survey meter. The results show that the effect may depend on several factors such as instrument design, alignment of the instrument axis with the magnetic flux lines, whether the instrument is stationary or moving relative to the magnetic field, the direction of the movement relative to the magnetic flux lines, and the magnetic field intensity. Also presented are results of work to enhance magnetic shielding of some of the instruments.


Persistent effects of the orexin-1 receptor antagonist SB-334867 on motivation for the fast acting opioid remifentanil.
The orexin (hypocretin) system is multifaceted, and regulates sleep-wake cycles, nociception, endocrine function and reward-seeking behavior. We have established an important role for this system in motivation for drugs of abuse. The orexin-1 receptor (Ox1R) antagonist SB334867 (SB) reduces seeking of drug reward under conditions of high motivation. There is some evidence that the effects of systemic SB on reward seeking persist beyond the pharmacological availability of the drug, however the time course of these effects is not well characterized, nor is it known whether similar persistent effects are observed following intraparenchymal injections. Here, we used a behavioral economics paradigm, which allows for repeated testing of drug motivation across consecutive days, to examine the persistent effects of acute systemic and local treatment with SB on motivation for the short-acting μ-opioid receptor agonistremifentanil. Systemic injections of SB immediately prior to behavioral testing reduced motivation for remifentanil; this effect was sustained on a subsequent test at 24 h, but not on a third test at 48 h. When injected into ventral pallidum (VP) the effects of SB were more persistent, with reduced motivation observed for up to 48 h. We next made SB injections into VP 24 h prior to behavioral testing; this produced effects that persisted for at least 72 h post-treatment. Cued reinstatement of extinguished remifentanil seeking was also attenuated by pretreatment with SB 24 h earlier. These data indicate that the effects of SB on opioid seeking behavior persist beyond the bioavailability of the compound. These observations have important ramifications for the future clinical use of orexin receptor antagonists for the treatment of addiction.


The excess of 5' introns in eukaryotic genomes.
In this work, 21 completely sequenced eukaryotic genomes were analyzed using an intragene comparison approach. We found that all of these genomes show a significant 5'-biased distribution of introns of protein-coding genes. Our findings are different from previous studies based on the intergene method, where introns are biased towards the 5' end of genes only in intron-poor genomes, but are evenly distributed in intron-rich genomes. In addition, by analyzing the patterns of intron distribution of a set of well-compiled housekeeping genes from human and their respective orthologs identified by a bidirectional best BLAST hit method from the other genomes, we found that the trend of 5'-biased intron positions of the set of housekeeping genes for each genome is much more skewed than that of all genes of the same genome, and rarely if any of the housekeeping genes examined have an extremely 3'-biased position distribution in which all introns of a gene are located only at the 3' portion of the gene. The most parsimonious explanation for our findings may be the model in which intron loss is caused by homologous recombination between the genomic copy of a gene and a reverse transcriptase product of a spliced mRNA.


Comparison of API20C with molecular identification of Candida spp isolated from bloodstream infections.
A study was carried out to compare the API20C technology with polymerase chain reaction amplification and direct sequencing of the short internal transcribed spacer region 2 (ITS2) for the identification of 58 isolates of invasive candida species obtained from patients with bloodstream infections over the seven year period 1994 to 2000. Overall, there was only one disagreement between the phenotypic and genotypic identification, where the API scheme identified the isolate as C albicans but the molecular method identified it as C dubliniensis. This study demonstrated that the API20C method is useful in the identification of Candida spp isolated from blood culture and that molecular methods do not enhance identifications made using the API20C scheme. However, for correct reporting of C dubliniensis, an emerging bloodborne pathogen, it is recommended that all isolates identified as C albicans by the API20C scheme are further examined phenotypically and/or genotypically.


The primary structures of one elicitor-active and seven elicitor-inactive hexa(beta-D-glucopyranosyl)-D-glucitols isolated from the mycelial walls of Phytophthora megasperma f. sp. glycinea.
The primary structures of eight hexa(beta-D-glucopyranosyl)-D-glucitols purified from partially hydrolyzed Phytophthora megasperma f. sp. glycinea mycelial walls were determined by microscale glycosyl-sequence analysis. The elicitor-active hexa(beta-D-glucopyranosyl)-D-glucitol had the following structure: (Formula: see text) The similarity in structure of six of the elicitor-inactive hexa(beta-D-glucopyranosyl)-D-glucitols to the elicitor-active hexa(beta-D-glucopyranosyl)-D-glucitol established that a highly defined structure is required for elicitor activity. The elicitor-active hexa(beta-D-glucopyranosyl)-D-glucitol is the first example of a complex carbohydrate acting as a regulatory molecule in plants.


Inhibition by actinomycin D of uridine diphosphoglucose synthetase activity during differentiation of Dictyostelium discoideum.
Actinomycin D inhibits the increase in specific activity of uridine diphosphoglucose synthetase during differentiation of the cellular slime mold, Dictyostelium discoideum. The degree to which this inhibition occurs is strictly correlated with, and may result from, the general inhibition of morphogenesis by actinomycin D.


[Transdiaphragmatic radiofrequency ablation of malignant liver tumors].
The majority of patients with primary or metastatic liver tumors are not candidates for resection because of the size, location, or multifocality of their tumors, or because of inadequate hepatic function related to cirrhosis. Radiofrequency ablation (RFA) is an evolving technique for treating patients with unresectable primary or metastatic liver cancers. After obtaining the approval of our institutional review board for this study, 12 patients with HCC and 6 patients with metastatic liver tumors were treated using the LeVeen RF ablation system at the Department of Surgery of Osaka National Hospital between March 2000 and February 2002. Informed consent was obtained from all patients. Ultrasound-guided RFA was done during open surgery. In 12 patients, RFA was performed during laparotomy, while in 6 patients it was done transdiaphragmatically during thoracotomy. All treated tumors showed complete necrosis on imaging after the completion of RFA. After a median follow-up period of 288 days, the tumor had recurred in 5 out of 18 patients, and the median overall survival rate was 362 days. No deaths or major complications occurred in these 18 patients. Liver function tests (ALT, AST, GGT) that were elevated after RFA returned to baseline in most patients by day 7. In 5 patients who underwent RFA at laparotomy, bile leakage and liver abscess developed. There were no cases of bile duct injury or liver abscess in the patients receiving transdiaphragmatic RFA. In conclusion, transdiaphragmatic RFA during thoracotomy is a safe, well-tolerated, effective treatment for unresectable hepatic malignancies.


Blood pressure and cardiovascular risk factors in women treated for climacteric symptoms with acupuncture, phytoestrogens, or hormones.
To evaluate the response of cardiovascular risk factors to the treatment of climacteric symptoms. In this prospective study, women reporting climacteric symptoms were randomized to 3 months of treatment with either acupuncture (n = 19), phytoestrogens (75 mg soy isoflavones, BID; n = 22), or low-dose hormone therapy (HT; 0.3 mg conjugated equine oestrogens plus 1.5 mg medroxyprogesterone acetate; n = 20). Greene's climacteric scale, blood pressure (BP), lipids, glucose, insulin, and homeostatic model assessment of insulin resistance were assessed before and after treatment. Observed changes were compared by analysis of variance. HT and acupuncture reduced Greene climacteric score to a similar extent, but the effect of phytoestrogens was significantly lower (P < 0.05). With acupuncture, systolic (-7.4 ± 15.3 mm Hg; P < 0.05) and diastolic BP (-8.3 ± 7.7mm Hg; P < 0.01) decreased, and the same occurred with phytoestrogens (-8.4 ± 9.0 mm Hg [P < 0.01] and -6.6 ± 7.9 mm Hg [P < 0.01]). Neither BP systolic (1.9 ± 17.5 mm Hg) nor BP diastolic (-1.4 ± 9.6 mm Hg) changed during HT. Low-density lipoprotein cholesterol decreased with phytoestrogens (-9.9 ± 19.6 mg/dL; P < 0.05), and triglycerides increased with both HT (34.5 ± 12.2 mg/dL; P < 0.01) and phytoestrogens (17.41 ± 24.4 mg/dL; P < 0.01). A slight but significant increase in homeostatic model assessment of insulin resistance (0.14 ± 0.5; P < 0.05) was observed after HT. Treatment of climacteric symptoms with acupuncture and phytoestrogens, but not HT, is associated with a clear BP reduction, and phytoestrogens with potentially positive alterations in low-density lipoprotein cholesterol level. EudractCT Number 2008-006053-41. : Video Summary:http://links.lww.com/MENO/A637.


Single-Cell Transcriptomics Reveals Peripheral Immune Responses in Anti-Synthetase Syndrome-Associated Interstitial Lung Disease.
Interstitial lung diseases (ILDs) secondary to anti-synthetase syndrome (ASS) greatly influence the prognoses of patients with ASS. Here we aimed to investigate the peripheral immune responses to understand the pathogenesis of this condition. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from 5 patients with ASS-ILD and 3 healthy donors (HDs). Flow cytometry of PBMCs was performed to replenish the results of scRNA-seq. We used scRNA-seq to depict a high-resolution visualization of cellular landscape in PBMCs from patients with ASS-ILD. Patients showed upregulated interferon responses among NK cells, monocytes, T cells, and B cells. And the ratio of effector memory CD8 T cells to naïve CD8 T cells was significantly higher in patients than that in HDs. Additionally, Th1, Th2, and Th17 cell differentiation signaling pathways were enriched in T cells. Flow cytometry analyses showed increased proportions of Th17 cells and Th2 cells, and decreased proportion of Th1 cells in patients with ASS-ILD when compared with HDs, evaluated by the expression patterns of chemokine receptors. The scRNA-seq data analyses reveal that ASS-ILD is characterized by upregulated interferon responses, altered CD8 T cell homeostasis, and involvement of differentiation signaling pathways of CD4 T cells. The flow cytometry analyses show that the proportions of Th17 cells and Th2 cells are increased and the proportion of Th1 cells is decreased in patients with ASS-ILD. These findings may provide foundations of novel therapeutic targets for patients with this condition.


pH-Sensitive Silver-Containing Carbon Dots Based on Folic Acid.
Herein, Ag-containing carbon dots (Ag-CDs) was synthesized based on folic acid. In a neutral solution, its fluorescence emission owns a structure fixing fluorescent species with the emission maximum at 400 nm and an excitation-wavelength dependent fluorescent species, respectively. By comparing fluorescent emission and excitation spectra, the electronic absorption origins of these fluorescent species were assigned. With the assistance of UV-Vis absorption and XPS, the pH-regulating fluorescence mechanism of Ag-CDs was studied and proposed. A particularly strong fluorescence emitter was observed at pH ~12 with a mixing coordination structure as Ag(CDs-NH2)OH. The as-prepared Ag-CDs might be developed into a fluorescent sensor, especially at extremely basic conditions.


Influence of feeding Tinospora cordifolia peripartum on lactation parameters in crossbred cows.
For studying the effect of dietary supplementation of guduchi (Tinospora cordifolia) peripartum on lactation an investigation was conducted on 15 pregnant Karan Fries crossbred cows which were divided into two groups: treatment group of eight cows which were supplemented with guduchi at 60 g/day for 45 days prepartum and 120 g/day for 45 days postpartum; control group of seven pregnant cows which were not supplemented with guduchi. Jugular blood samples were collected from all cows during the periparturient period for analysis of various blood cell and plasma parameters. A significantly higher total leukocyte count, lymphocyte count, neutrophil count and neutrophil/lymphocyte ratio was recorded in the guduchi supplemented treatment group in comparison to untreated control cows throughout the experimental period. The increase of milk production over 305 days of lactation due to guduchi supplementation was significant (p < 0.05). A significant (p < 0.05) reduction in somatic cell count was also observed during the experimental period. Milk composition (fat, protein, lactose and SNF) was similar (p > 0.05) for both the groups. Plasma non esterified fatty acid (NEFA) concentrations were significantly higher (p < 0.01) in cows supplemented with guduchi throughout the course of study. Plasma concentration of growth hormone in the treated cows was also significantly higher beginning on the day of parturition up to 3 weeks postpartum (p < 0.05) in comparison to unsupplemented group.


Progression in keratoconus and the effect of corneal cross-linking on progression.
Ultraviolet corneal collagen cross-linking (CXL) has been shown to possibly delay, halt, or even reverse disease progression in keratoconus. Understanding of keratoconic progression in untreated eyes, however, is still incomplete and is hampered by the varying definitions and metrics used to evaluate corneal changes. As a result, the CXL literature varies widely in criteria for progression and parameters for successful outcomes. To date, there have been few long-term, well-controlled clinical trials supporting the efficacy of CXL to prevent progression in keratoconus. Review of our data on keratoconus suggests the course of corneal change is difficult to predict and that many keratoconic eyes appear stable once the eyes begin to exhibit frank changes in corneal curvature typical of keratoconus. Better-defined metrics for progression in keratoconus are needed. Larger, long-term randomized clinical trials may more clearly establish the efficacy and safety of CXL in the management of keratoconus and determine which patients are the best candidates for this procedure.


Conformation-dependent inhibition of gastric H+,K+-ATPase by SCH 28080 demonstrated by mutagenesis of glutamic acid 820.
Gastric H+,K+-ATPase can be inhibited by imidazo pyridines like 2-methyl-8-[phenylmethoxy] imidazo-(1,2a) pyridine 3-acetonitrile (SCH 28080). The drug shows a high affinity for inhibition of K+-activated ATPase and for prevention of ATP phosphorylation. The inhibition by SCH 28080 can be explained by assuming that SCH 28080 binds to both the E2 and the phosphorylated intermediate (E2-P) forms of the enzyme. We observed recently that some mutants, in which glutamic acid 820 present in transmembrane domain six of the catalytic subunit had been replaced (E820Q, E820N, E820A), lost their K+-sensitivity and showed constitutive ATPase activity. This ATPase activity could be inhibited by similar SCH 28080 concentrations as the K+-activated ATPase of the wild-type enzyme. SCH 28080 also inhibited ATP phosphorylation at 21 degrees C of the mutants E820D, E820N, and E820A, although with varying efficacy and affinity. ATP-phosphorylation of mutant E820Q was not inhibited by SCH 28080; in contrast, the phosphorylation level at 21 degrees C was nearly doubled. These findings can be explained by assuming that mutation of Glu820 favors the E1 conformation in the order E820Q >E820A >E820N >wild-type = E820D. The increase in the phosphorylation level of the E820Q mutant can be explained by assuming that during the catalytic cycle the E2-P intermediate forms a complex with SCH 28080. This intermediate hydrolyzes considerably slower than E2-P and thus accumulates. The high tendency of the E820Q mutant for the E1 form is further supported by experiments showing that ATP phosphorylation of this mutant is rather insensitive towards vanadate, inorganic phosphate, and K+.


[Study of the Relationship between Oral Diseases and Depression Symptoms in Middle-Aged and Older Adult Populations in China-A Retrospective Study Based on CHARLS Data].
To study the relationship between oral disease and depressive symptoms in middle-aged and older adult populations in China. The data from the China Health and Retirement Longitudinal Study (CHARLS) done between 2013 and 2015 were analyzed. A total of 3828 middle-aged and older adults showing no depressive symptoms in an assessment with the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10) were selected as the subjects of observation, and oral disease was taken as the dependent variable. Changes in depressive symptoms in the population were tracked in 2015, and the Cox proportional hazards model was used to estimate the relationship between oral diseases and depressive symptoms. The detection rate of depressive symptoms was 29.3% in middle-aged and older adults with oral diseases, and that of middle-aged and older adults without oral diseases was 20.4%, the difference being statistically significant ( P<0.001). After controlling for confounding factors, Cox proportional hazards model analysis found an association between oral diseases and depressive symptoms (hazard ratio [ HR]=0.683, 95% confidence interval [ CI]: 0.583-0.800). It was more likely for middle-aged and older women ( HR=0.708, 95% CI: 0.573-0.874) with oral diseases to develop depressive symptoms than men ( HR=0.644, 95% CI: 0.506-0.819) did ( P<0.05). Oral diseases in the middle-aged and older adult populations tended to lead to depressive symptoms, and women showed higher rate than men did. Prevention and control measures should be taken actively in the course of oral disease treatment to promote mental health of middle-aged and older adults.


Recombinant Trichomonas vaginalis eIF-5A protein expressed from a eukaryotic system binds specifically to mammalian and putative trichomonal eIF-5A response elements (EREs).
Trichomonas vaginalis eIF-5A-like protein (TveIF-5A) belongs to the highly conserved eIF-5A family of proteins that contains a unique polyamine-derived amino acid, hypusine. Recently, we determined that the polyamine putrescine is required for tveif-5a mRNA stability, and it is necessary for stability and maturation of the TveIF-5A protein. Eukaryotic eIF-5A is known to be involved in mRNA turnover and is capable of sequence-specific RNA binding to eIF-5A response elements (EREs). These ERE sequences are present in diverse mammalian mRNAs, including human cyclooxygenase-2 (cox-2). Here, we cloned the complete coding sequence of TveIF-5A and overexpressed it in a eukaryotic system. The recombinant protein (rTveIF-5A) was purified in soluble form using size-exclusion chromatography. Because of the polyamine-dependent regulation of TvCP39 (a protease of T. vaginalis) at the protein and RNA messenger (mRNA) levels, we looked for an ERE-like structure in the 3' region of tvcp39 mRNA. In RNA gel-shift assays, rTveIF-5A bound to transcripts at the EREs of cox-2 or tvcp39 mRNAs. This work shows the eIF-5A/ERE-like interaction in T. vaginalis.


Effects of vibration and passive resting on muscle stiffness and restitution after submaximal exercise analyzed by elastography.
The research aimed to assess the influence of vibration therapy on acceleration of muscles regeneration process after physical effort. Verification of the pace of motor capabilities recovery in fatigued muscles was performed with the use of the measurement method applying shear-wave elastography. It took into account an alteration in muscle stiffness affected by created passive stresses and accompanying deformations connected with muscles work above their resting length. The research included 42 young males aged 20-24. They all were a homogeneous group regarding body build indices (body height 175.4 ± 8.1 cm; body mass 75.5 ± 8.32 kg) and the level of physical activity. Muscles of lower limbs (hip and knee joints extensors and flexors plantaris) were subject to submaximal exercise of the auxotonic muscle work character after a 90 s warm-up. The exercise comprised 20-fold overcoming the load at the level of 75% of maximal strength abilities without rest, by alternating between extension and flexion of lower limbs joints at the leg press placed at 45° angle upward and monitoring of angle setting of lower limbs joints. The post-exercise restitution used a vibration stimulus of variable frequency ranging from 20 to 50 Hz and amplitude of 0.5 mm, and passive resting in the control group. For an objective assessment of the applied vibration effect, a 5-fold measurement of rectus femoris muscles stiffness of both limbs at the middle of venter took place after each stage of the experiment. After warm-up, a considerable increase of the examined muscles stiffness, that did not vary significantly, was observed. In the DW experimental group (vibration massage), where post-exercise restitution was enhanced by vibration, significantly lower values of muscle stiffness were registered after each of the post-exercise regeneration stages in relation to the DB control group (passive rest). After the I regeneration stage, a value of the Δσ_r1-s variable ( p < 0.05) lower by 16% was noticed in favour of the group enhanced by vibration. Whereas, values of muscles stiffness after the II stage of regeneration, Δσ_r2-s were by 14% lower in favour of DW group ( p < 0.005). Enhancement of the post-exercise relaxation of muscles by vibration treatment significantly lowered the values of post-exercise muscles stiffness and turned out to be a more effective method of restitution than passive resting. Recovery of the level of muscles stiffness from before the exercise was much slower in the control group than in the one enhanced by vibration. The improved method of muscle stiffness measurement with the use of shear-wave elastography with a special head attachment turned out to be a useful tool to assess post-exercise muscles restitution.