title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
|---|---|---|
Impact of preoperative anxiolytic on surgical site infection in patients undergoing abdominal hysterectomy. | An increased anxiety may be associated with a higher risk of surgical site infection (SSI), but there is little objective data on the effect of preoperative anxiolytic interventions on SSI. To address this issue, we evaluated the effects of preoperative diazepam on postoperative SSI following abdominal hysterectomy. This randomized, double-blinded, placebo-controlled study included 130 patients, American Society of Anesthesiologist physical status 1 or 2. Patients were randomly assigned to receive either oral diazepam 10 mg (n = 65) or placebo (n = 65) the night before and 1 hour prior to surgery. The assessment instruments were the Visual Analogue Scale and the State-Trait Anxiety Inventory. SSI was diagnosed according to the criteria of the Centers for Disease Control and Prevention with standard follow-up of 30 days. The relative risk (RR) was 1.79 (95% confidence interval [CI]: 1.31-2.43), and the number of patients that needed to be treated was 5.2 (95% CI: 2.74-50.76) to prevent 1 additional SSI. The RR for SSI in placebo-treated patients with high postoperative anxiety was 1.65 (95% CI: 1.07-2.56). Diazepam-treated patients showed lower postoperative anxiety and lower incidence of SSI up to 30 days after surgery compared with placebo in patients undergoing abdominal hysterectomy. | 18,834,731 |
The association between handwashing practices and illness symptoms among college students living in a university dormitory. | We describe handwashing practices, the association of handwashing with upper respiratory and gastrointestinal symptoms, and the effects of gender on handwashing practices among male (n = 215) and female (n = 243) college students. Self-reported frequency of handwashing was not associated with infectious illness symptom reporting. Only a small proportion of males (10%) and females (7%) reported "always" washing their hands before eating. Females were more likely than males to always wash their hands after urinating (69% vs 43%; P < .0001) and after a bowel movement (84% vs 78%; P = .14). Identifying new strategies to increase handwashing may help prevent infectious disease transmission in residence hall environments. | 18,834,732 |
Religion and culture: potential undercurrents influencing hand hygiene promotion in health care. | Health care-associated infections affect hundreds of millions of patients worldwide each year. The World Health Organization's (WHO) First Global Patient Safety Challenge, "Clean Care is Safer Care," is tackling this major patient safety problem, with the promotion of hand hygiene in health care as the project's cornerstone. WHO Guidelines on Hand Hygiene in Healthcare have been prepared by a large group of international experts and are currently in a pilot-test phase to assess feasibility and acceptability in different health care settings worldwide. An extensive literature search was conducted and experts and religious authorities were consulted to investigate religiocultural factors that may potentially influence hand hygiene promotion, offer possible solutions, and suggest areas for future research. Religious faith and culture can strongly influence hand hygiene behavior in health care workers and potentially affect compliance with best practices. Interesting data were retrieved on specific indications for hand cleansing according to the 7 main religions worldwide, interpretation of hand gestures, the concept of "visibly dirty" hands, and the use of alcohol-based hand rubs and prohibition of alcohol use by some religions. The impact of religious faith and cultural specificities must be taken into consideration when implementing a multimodal strategy to promote hand hygiene on a global scale. | 18,834,738 |
Consideration to culture health care workers related to increased methicillin-resistant Staphylococcus aureus activity in a neonatal intensive care unit. | For 2 consecutive years, a care level III neonatal intensive care unit (NICU) in a 700-bed health care facility experienced an increase in health care-associated methicillin-resistant Staphylococcus aureus (MRSA). To decrease transmission, standard infection prevention techniques, active surveillance cultures, and deoxyribonucleic acid typing were done. After control was achieved, members of the organization outside of infection prevention and control requested health care worker (HCW) screening for MRSA, believing that it would decrease chances of future transmission. To develop effective tools to communicate with organization members: (1) questions that must be resolved before HCW screening can be done accurately, (2) operational requirements for HCW screening, and (3) a "trigger point" for HCW screening should MRSA activity increase in the future. Developed tools to determine when MRSA screening of HCWs is warranted and for the preparation process when MRSA screening is necessary. Without performing HCW screening in the NICU, there were no health care-associated infections with MRSA for 20 months or colonization for 5 months. Proactive consideration of HCW screening can be achieved by designing and implementing tools to illustrate the complexity of the HCW screening process and by defining a "trigger point" for HCW culturing if needed for MRSA control. Decreasing MRSA transmission in this NICU was accomplished without culturing health care workers. | 18,834,741 |
Evaluation of patient participation in a patient empowerment initiative to improve hand hygiene practices in a Veterans Affairs medical center. | In patient empowerment initiatives, patients are encouraged to ask caregivers if they have washed their hands. However, relatively little is known about the willingness of patients to participate in such initiatives. Patients were presented with a "Partners in Your Care" script asking them to remind health care workers to wash their hands, and follow-up interviews were conducted. Compliance was reassessed using a modified script in which patients were asked to thank health care workers for washing and/or to display a sign stating "Thanks for Washing." Of the 193 patients presented with the initial script, 5 (3%) stated that they had reminded health care workers to wash, and 15 (8%) had not commented despite observing health care workers failing to wash in their presence. Of the 38 patients given the modified script instructing them to thank health care workers for washing, 17 (45%) reported mentioning hand hygiene to health care workers (13 of whom thanked the caregivers), and 6 (16%) did not comment despite observing health care workers failing to wash in their presence. Most patients displayed a sign thanking caregivers for washing; however, no patients were observed to comment on hand hygiene during physician work rounds, and only 2 of 30 (7%) nurses on the study wards reported being thanked for washing. In this Veterans Affairs hospital, patients were unlikely to remind health care workers to wash their hands. Patient empowerment initiatives may be more effective if patients are encouraged to provide positive reinforcement and/or display prompting visual reminders. | 18,834,750 |
WITHDRAWN: Retrocardiac Sponge-Induced Hemodynamic Instability in the Postcardiopulmonary Bypass Period: Detection by Transesophageal Echocardiography. | The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1053/j.jvca.2008.11.012. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. | 18,834,782 |
The relationship between carotid blood-flow velocity and the left ventricular area during acute regional ischemia. | Myocardial contractility can be described by the relationship between blood-flow velocity in the carotid artery and the left ventricular cross-sectional area. The authors investigated whether critical myocardial ischemia influences the derived contractility index, E'(es). A prospective animal study. A university research laboratory. Eleven Göttinger minipigs. Within the closed-chest model, the authors placed a U-shaped 8-MHz miniature Doppler probe around the left internal carotid artery and inserted a combined pressure-conductance catheter into the left ventricular cavity via the right internal carotid artery. A balloon occlusion catheter was placed into the inferior caval vein from a femoral vein and acquired transthoracic-view echocardiographic images. An active coronary perfusion catheter was positioned in the proximal left circumflex coronary (LCx) artery. The LCx bed was perfused with blood from the contralateral femoral artery by using a high-precision-output roller pump. Stage analysis during normal perfusion revealed evidence for the following function: E'(es) = 0.066 + 0.121 E(es) (R = 0.96, R(2) = 0.92, and p < 0.0001), which agrees with previously determined equations. Under ischemic conditions, the relationship changed to E'(es) = 0.048 + 0.196.E(es) (R = 0.83, R(2) = 0.69, and p < 0.0001). The limits of precision to detect changes in contractility by E'(es) increased from 16% to 45%; the bias did not notably deviate from zero. The indexes of mechanical dyssynchrony (mechanical dyssynchrony and internal flow fraction) derived from conductance catheter measurements increased significantly. The ability of E'(es) to indicate contractility during acute reduced coronary blood flow is limited. | 18,834,794 |
Site-specific labeling of T7 DNA polymerase with a conformationally sensitive fluorophore and its use in detecting single-nucleotide polymorphisms. | Like most enzymes, DNA polymerases undergo a large conformational change on the binding of a correct nucleotide. To determine how the conformational change contributes to substrate specificity, we labeled the T7 DNA polymerase with a conformationally sensitive fluorophore at a position that provides a signal coincident with structural changes following nucleotide binding and distinguishes correct base pairs from incorrect ones by the sign of the fluorescence change. Here we describe methods to document that only one site on the polymerase was labeled with the fluorophore based on mass spectral analysis of tryptic peptides. In addition, we show by equilibrium titrations of opposing signals that mismatches and correct bases compete for the same site. This analysis forms an essential basis for characterization of a fluorescently labeled enzyme intended for mechanistic studies. Finally, we show that the labeled enzyme can be used to identify single-nucleotide mutations in a procedure that could be automated. | 18,834,851 |
Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. | Tumor suppressor p53 transcriptionally regulates expression of microRNA-34a, which confers translational inhibition and mRNA degradation of genes involved in cell cycle control and apoptosis. In various cancers, miR-34a expression is lost or reduced. Here, we investigated the role of miR-34a in prostate cancer cell lines. MiR-34a expression was markedly reduced in p53-null PC3 cells and p53-mutated DU145 cells compared with LNCaP cells expressing wild-type p53. In PC3 cell, ectopic expression of miR-34a decreased the SIRT1 mRNA and protein levels as well as protein levels of known direct target genes. Reporter assays revealed that miR-34a-induced SIRT1 inhibition occurred at the transcriptional but not post-transcriptional level despite the presence of a potential miR-34a binding site within its 3'-UTR. Ectopic miR-34a expression resulted in cell cycle arrest and growth inhibition and attenuated chemoresistance to anticancer drug camptothecin by inducing apoptosis, suggesting a potential role of miR-34a for the treatment of p53-defective prostate cancer. | 18,834,855 |
The cell growth suppressor, mir-126, targets IRS-1. | miRNAs are a family of approximately 22-nuleotide-long noncoding RNAs involved in the formation and progress of tumors. Since traditional methods for the detection of miRNAs expression have many disadvantages, we developed a simple method called polyA RT PCR. With this method, we detected a series of miRNAs and found that mir-126 is one of the miRNAs underexpressed in breast cancer cells. Flow cytometry analysis showed that mir-126 inhibited cell cycle progression from G1/G0 to S. Further studies revealed that mir-126 targeted IRS-1 at the translation level. Knocking down of IRS-1 suppresses cell growth in HEK293 and breast cancer cell MCF-7, which recapitulates the effects of mir-126. In conclusion, we developed a simple method for high-throughput screening of miRNAs and found that mir-126, a cell growth suppressor, targets IRS-1. | 18,834,857 |
A high contrast method of unstained biological samples under a thin carbon film by scanning electron microscopy. | The contrast of biological samples in scanning electron microscopy (SEM) is very weak. To examine a biological specimen by SEM, many steps and/or special equipment are required to prepare the sample. Here, we describe a method using an unstained biological sample under a 40 nm carbon film to give a high contrast image, where the image is detected by the secondary electron (SE) signal at a low accelerating voltage of 1.5 kV. Under these conditions, it is hard to detect a direct signal from a biological specimen. The high contrast image is created by the SEs from the lower surface of the thin carbon film. Therefore, the damage to the sample from the electron beam is very low. Our method can be utilized to observe various biological samples of bacteria, viruses, and protein complexes. | 18,834,858 |
Spinophilin inhibits the binding of RGS8 to M1-mAChR but enhances the regulatory function of RGS8. | We showed previously that RGS8 directly binds to the third intracellular loop (i3L) of the M1 muscarinic acetylcholine receptor using the sequence MPRR at the N-terminus of RGS8 and specifically inhibits signal transduction. Here, we identified spinophilin (SPL) as an RGS8-interacting protein. We found that the SPL-binding site of RGS8 is the MPRR sequence, and the M1 receptor and SPL compete for binding to RGS8. However, we also observed that the expression of SPL significantly enhances the inhibitory function of RGS8, and that SPL can bind to the M1 receptor, demonstrating the indirect binding of RGS8 to the M1 receptor through SPL for an efficient regulatory function. | 18,834,863 |
Effects of different extenders on DNA integrity of boar spermatozoa following freezing-thawing. | The sperm-rich fraction, collected from eight mature Yorkshire boars, was frozen in an extender containing 9% LDL (w/v), 100mM trehalose, or 20% yolk (v/v), respectively. Sperm DNA integrity was assessed using the single-cell gel electrophoresis (SCGE). Other sperm quality characteristics such as motility, acrosome and membrane integrity were also monitored. The results showed that freezing-thawing caused an increase in sperm DNA fragmentation, and extender containing 9% LDL could significantly protect sperm DNA integrity (P<0.05) from the damage caused by cryopreservation and decrease DNA damages compared with extender containing 100mM trehalose and 20% yolk (v/v). No significant difference in damaged DNA was detected between frozen and unfrozen semen samples for extender of 9% LDL and 100mM trehalose, but cryopreservation could increase the degree of DNA damage (P<0.05), the percentage of damaged DNA degree of grade 2 and 3 was significantly increased. The deterioration in post-thaw sperm DNA integrity was concurrent with reduced sperm characteristics. The data here demonstrated that the cryoprotectant played a fundamental role in reducing boar sperm DNA damage and protecting DNA integrity. It can be suggested that evaluation of sperm DNA integrity, coupled with correlative and basic characteristics such as motility, acrosome integrity and membrane integrity, may aid in determining the quality of frozen boar semen. | 18,834,872 |
Bayesian surprise attracts human attention. | We propose a formal Bayesian definition of surprise to capture subjective aspects of sensory information. Surprise measures how data affects an observer, in terms of differences between posterior and prior beliefs about the world. Only data observations which substantially affect the observer's beliefs yield surprise, irrespectively of how rare or informative in Shannon's sense these observations are. We test the framework by quantifying the extent to which humans may orient attention and gaze towards surprising events or items while watching television. To this end, we implement a simple computational model where a low-level, sensory form of surprise is computed by simple simulated early visual neurons. Bayesian surprise is a strong attractor of human attention, with 72% of all gaze shifts directed towards locations more surprising than the average, a figure rising to 84% when focusing the analysis onto regions simultaneously selected by all observers. The proposed theory of surprise is applicable across different spatio-temporal scales, modalities, and levels of abstraction. | 18,834,898 |
Protective effects of IRFI-042 in monensin induced neurotoxicity in chicks. | Monensin, a well known ionophore antibiotic, may cause severe damage in neuronal cells by altering Na+/K+-ATPase and Ca2+-ATPase. We investigated whether IRFI-042, a synthetic analogue of vitamin E, may block lipid peroxidation in neuronal cells and protect against monensin neurotoxicity in chicks. Monensin toxicity was induced in chicks by once-daily administration (150 mg/kg by oral gavages), for 8 days. Sham animals received a saline solution and were used as controls. All animals were randomized to receive either IRFI-042 (20 mg/kg) or its vehicle. Survival rate, brain lipid peroxidation, mRNA for neuronal and inducible nitric oxide synthases (nNOS and iNOS) and brain histological evaluations, including immunohistochemical expression of nNOS and iNOS were performed. Monensin administration decreased survival rate, induced behavioural changes, increased brain lipid peroxidation, reduced brain nNOS mRNA and immunostaining and enhanced iNOS mRNA and immunostaining in the brain in chicks. IRFI-042 significantly improved the survival rate and counteracted monensin-induced changes in chick brains. Our data suggest that monensin is responsible of neurotoxicity in chicks by inducing oxidative stress/lipid peroxidation and that IRFI-042 might represent a useful pharmacological approach to protect against the neuronal damage induced by this monovalent carboxylic ionophorous polyether antibiotic. | 18,834,916 |
Electroacupuncture decreases nitric oxide synthesis in the hypothalamus of spontaneously hypertensive rats. | Acupuncture-related effects on autonomic function have been explored via biological and neurophysiologic studies. The hypothalamus, known to regulate the autonomic nervous system, is likely affected by acupuncture treatment that modulates sympathetic functions. The aim of this study was to investigate the effect of electroacupuncture at the Jogsamni point (ST36, an acupoint known to modulate autonomic function) on expression of neuronal nitric oxide synthase (nNOS) in the hypothalamus of spontaneously hypertensive rat. Nitric oxide, which is produced by nNOS activity, plays an important role in the regulation of many physiologic processes, including sympathetic activities, in the hypothalamus and other parts of the brain. nNOS expression was assessed by immunohistochemistry of nNOS and histochemistry of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d). The staining intensities of nNOS-positive neurons and NADPH-d-positive neurons were quantitatively assessed using microdensitometry to measure changes in optical density. The results show that electroacupuncture at ST36 reduced the expression and activity of nNOS in the hypothalamus of spontaneously hypertensitive rats. These findings suggest that the electroacupuncture at ST36 results in modulation of the activity of nNOS in the hypothalamus of spontaneously hypertensive rat. | 18,834,924 |
Olfactory sensory deprivation increases the number of proBDNF-immunoreactive mitral cells in the olfactory bulb of mice. | In the olfactory bulb, apoptotic cell-death induced by sensory deprivation is restricted to interneurons in the glomerular and granule cell layers, and to a lesser extent in the external plexiform layer, whereas mitral cells do not typically undergo apoptosis. With the goal to understand whether brain-derived neurotrophic factor (BDNF) mediates mitral cell survival, we performed unilateral naris occlusion on mice at postnatal day one (P1) and examined the subsequent BDNF-immunoreactive (BDNF-ir) profile of the olfactory bulb at P20, P30, and P40. Ipsilateral to the naris occlusion, there was a significant increase in the number of BDNF-ir mitral cells per unit area that was independent of the duration of the sensory deprivation induced by occlusion. The number of BDNF-ir juxtaglomerular cells per unit area, however, was clearly diminished. Western blot analysis revealed the presence of primarily proBDNF in the olfactory bulb. These data provide evidence for a neurotrophic role of proBDNF in the olfactory system of mice and suggest that proBDNF may act to protect mitral cells from the effects of apoptotic changes induced by odor sensory deprivation. | 18,834,927 |
Studies on the immunomodulatory effect of extract of Cyanodon dactylon in shrimp, Penaeus monodon, and its efficacy to protect the shrimp from white spot syndrome virus (WSSV). | The present study investigates the protection of shrimp Penaeus monodon against white spot syndrome virus (WSSV) using antiviral plant extract derived from Cyanodon dactylon and the modulation of the shrimp non-specific immunity. To determine the antiviral activity, the shrimp were treated by both in vitro (intramuscular injection) and in vivo (orally with feed) methods at the concentration of 2mg per animal and 2% of the plant extract incorporated with commercially available artificial pellet feed, respectively. The antiviral activity of C. dactylon plant extract was confirmed by PCR, bioassay and Western blot analysis. In the present study, anti-WSSV activity of C. dactylon plant extract by in vivo and in vitro methods showed strong antiviral activity and the immunological parameters such as proPO, O(2)(-), NO, THC and clotting time were all significantly (P<0.05) higher in the WSSV-infected shrimp treated with plant extract when compared to control groups. These results strongly indicate that in vivo and in vitro administration of C. dactylon plant extract enhances immunity of the shrimp. Based on the present data and the advantages of plant extract available at low price, we believe that oral administration of C. dactylon plant extract along with the pellet feed is a potential prophylactic agent against WSSV infection of shrimp. | 18,834,943 |
Electrostatically constrained alpha-helical peptide inhibits replication of HIV-1 resistant to enfuvirtide. | Alpha-helical peptides, such as T-20 (enfuvirtide) and C34, derived from the gp41 carboxyl-terminal heptad repeat (C-HR) of HIV-1, inhibit membrane fusion of HIV-1 and the target cells. Although T-20 effectively suppresses the replication of multi-drug resistant HIV variants both in vitro and in vivo, prolonged therapy with T-20 induces emergence of T-20 resistant variants. In order to suppress the emergence of such resistant variants, we introduced charged and hydrophilic amino acids, glutamic acid (E) and lysine (K), at the solvent accessible site of C34. In particular, the modified peptide, SC34EK, demonstrates remarkably potent inhibition of membrane fusion by the resistant HIV-1 variants as well as wild-type viruses. The activity was specific to HIV-1 and little influenced by serum components. We found a strong correlation between the anti-HIV-1 activities of these peptides and the thermostabilities of the 6-helix bundles that are formed with these peptides. We also obtained the crystal structure of SC34EK in complex with a 36 amino acid sequence (N36) comprising the amino-terminal heptad repeat of HIV-1. The EK substitutions in the sequence of SC34EK were directed toward the solvent and generated an electrostatic potential, which may result in enhanced alpha-helicity of the peptide inhibitor. The 6-helix bundle complex of SC34EK with N36 appears to be structurally similar to that of C34 and N36. Our approach to enhancing alpha-helicity of the peptide inhibitor may enable future design of highly effective and specific HIV-1 inhibitors. | 18,834,950 |
RAD51 foci formation in response to DNA damage is modulated by TIP49. | Chromatin modification plays an important role in modulating the access of homologous recombination proteins to the sites of DNA damage. TIP49 is highly conserved component of chromatin modification/remodeling complexes, but its involvement in homologous recombination repair in mammalian cells has not been examined in details. In the present communication we studied the role of TIP49 in recruitment of the key homologous recombination protein RAD51 to sites of DNA damage. RAD51 redistribution to chromatin and nuclear foci formation induced by double-strand breaks and interstrand crosslinks were followed under conditions of TIP49 depletion by RNA interference. TIP49 silencing reduced RAD51 recruitment to chromatin and nuclear foci formation to about 50% of that of the control. Silencing of TIP48, which is closely related to TIP49, induced a similar reduction in RAD51 foci formation. RAD51 foci reduction in TIP49-silenced cells was not a result of defective DNA damage checkpoint signaling as judged by the normal histone H2AX phosphorylation and cell cycle distribution. Treatment with the histone deacetylase inhibitor sodium butyrate restored RAD51 foci formation in the TIP49-depleted cells. The results suggest that as a constituent of chromatin modification complexes TIP49 may facilitate the access of the repair machinery to the sites of DNA damage. | 18,834,951 |
DNA methylomes, histone codes and miRNAs: tying it all together. | Our current knowledge of the deregulation that occurs during the onset and progression of cancer and other diseases leads us to recognize both genetic and epigenetic alterations as being at the core of the pathological state. The epigenetic landscape includes a variety of covalent modifications that affect the methylation status of DNA but also the post-translational modifications of histones, and determines the structural features of chromatin that ultimately control the transcriptional outcome of the cell to accommodate developmental, proliferative or environmental requirements. MicroRNAs are small non-coding RNAs that regulate the expression of complementary messenger RNAs and function as key controllers in a myriad of cellular processes, including proliferation, differentiation and apoptosis. In the last few years, increasing evidence has indicated that a substantial number of microRNA genes are subjected to epigenetic alterations, resulting in aberrant patterns of expression upon the occurrence of cancer. In this review we discuss microRNA genes that are epigenetically modified in cancer cells, and the role that microRNAs themselves can have as chromatin modifiers. | 18,834,952 |
Mutual modulation between interleukin-10 and interleukin-6 induced by Rhodococcus aurantiacus infection in mice. | The interaction between interleukin-10 (IL-10) and interleukin-6 (IL-6) was investigated in the inflammatory response to Rhodococcus aurantiacus (R. aurantiacus) infection, in which both cytokines act as anti-inflammatory cytokines. Compared with wild-type (WT) counterparts, IL-6 gene-deficient (IL-6(-)/(-)) mice mounted a more robust production of IL-10 and tumor necrosis factor-alpha (TNF-alpha) during the initial phase of infection. Administration of anti-IL-10 antibody resulted in all the mice dying within 3 days post-infection as well as a further elevated TNF-alpha release. In vitro challenge of the macrophages from IL-6(-)/(-) and WT mice with heat-killed R. aurantiacus also showed similar results. Addition of exogenous IL-6 depressed IL-10 and TNF-alpha production by either IL-6(-)/(-) mice or IL-6(-)/(-) mouse macrophages. Likewise, WT mouse macrophages pretreated with anti-IL-10 or anti-IL-6 antibody exhibited increased production of TNF-alpha and IL-6 or IL-10 respectively. Moreover, neutralization of both IL-10 and IL-6 induced a further increase in TNF-alpha production by WT mouse cells. Overall, we conclude that IL-10 is a key element in protecting mice against mortality, and that IL-10 and IL-6 production are negatively regulated by each other although they are additive in suppressing TNF-alpha release in R. aurantiacus-infected mouse model. | 18,834,949 |
Risk factors for elevated blood lead levels among African refugee children in New Hampshire, 2004. | Surveillance blood lead screening of refugee children resettled in Manchester, NH, in 2004 revealed that 39 (42%) of 92 children had elevated levels (>or=10 microg/dL) after resettlement. Furthermore, 27/92 children (29%) had nonelevated screening blood lead levels on arrival (BLL1) but had elevated follow-up blood lead levels 3-6 months after settlement (BLL2). The main objective was to identify risk factors for increasing lead levels among refugee children after resettlement in Manchester in 2004. We conducted a cohort study, with completion of household interviews and home assessments for refugee families who had resettled in 2004 in Manchester, NH. Blood lead level (BLL) data were abstracted from the New Hampshire (NH) Childhood Lead Poisoning Prevention Program. To assess acute and chronic malnutrition among refugees, we used anthropometric data from International Organization of Migration documents to calculate nutritional indices. Of the 93 African refugee children in 42 families who participated, 60 (65%) had been born in a refugee camp. Median age was 5.5 years at the time of BLL2 measurement. Thirty-six (39%) of the refugee children had BLL2 >or= 10 microg/dL. Liberians and those born in refugee camps had higher geometric mean BLL2 than those not Liberian or not born in camps. Younger children and children with nutritional wasting before immigrating to the United States had a greater increase in geometric mean from BLL1 to BLL2, compared to older children and those without nutritional wasting. Follow-up blood lead testing of refugee children, particularly those resettled in areas with older housing stock, as in Manchester, is important for identifying lead exposure occurring after resettlement. Increased attention to improve nutritional status of children in refugee camps and after arrival in the United States and awareness of children who were born in refugee camps should be incorporated into lead-poisoning prevention strategies. | 18,834,979 |
Acute arterial thrombosis in the absence of inflammation: the stress-related anti-inflammatory hormone ACTH participates in platelet-mediated thrombosis. | Despite the reciprocal relationship that exists between inflammation and thrombosis, we asked whether thrombosis can develop without inflammation, and whether stress-related hormones (ACTH and cortisol) influence platelet-mediated thrombosis. We investigated the role of ACTH and cortisol in platelet aggregation, as well as on the circulating levels of IL-6 in pigs subjected to different treatments. In control animals, deep vessel wall injury (DVWI) was induced in the right common carotid artery, while in the animals under study DVWI was induced 60 min after ACTH administration (subgroup 1) or not at all (subgroup 2). In an ex vivo study we evaluated whether ACTH or cortisol modulates platelet aggregation. Indeed, we assessed whether blocking the P2Y platelet receptors inhibits the effect of ACTH on platelet aggregation. Finally, we assessed whether ACTH mobilizes intracellular calcium and modulates intracellular cAMP in platelets ex vivo. We found that the suppression of inflammation following ACTH administration was accompanied by acute arterial thrombosis in the zone of injury in vivo. Furthermore, ACTH but not cortisol amplifies the platelet aggregation induced ex vivo by agonists. Platelets do not express ACTH receptors which may explain why ACTH does not reduce intracellular levels of cAMP in platelets. Nevertheless, supraphysiological concentrations of ACTH increase calcium mobilization in platelets. These results indicate for the first time that ACTH may fulfil an important role in acute arterial thrombosis by increasing the platelet aggregation induced by agonists, probably via a G(q)-coupled pathway. | 18,834,983 |
The pleiotropic effects of statins on endothelial function, vascular inflammation, immunomodulation and thrombogenesis. | Statins have been demonstrated to significantly affect the prognosis and outcome of patients with risk factors to atherosclerosis (in primary and secondary prevention trials). Several clinical and recently basic studies have suggested an extra-beneficial effect of the statins in the prevention of atherosclerosis and coronary artery disease. These studies showed that statins may affect the cardiovascular system beyond their effect on the lipid profile, and it was suggested that they affect the immunological system and vascular inflammation. Many of the beneficial pleiotropic effects of statins occur as a result of modulated endothelial function and reduced inflammatory processes. Attempting to understand these properties of statins is an exciting field of research that will also improve our understanding of vascular biology in health and disease, and thus enable the better use of this drug class in clinical practice. | 18,834,985 |
Kaolinite flocculation structure. | Effective flocculation and dewatering of mineral processing streams containing colloidal clays has become increasingly urgent. Release of water from slurries in tailings streams and dam beds for recycle water consumption, is usually slow and incomplete. To achieve fast settling and minimization of retained water, individual particles need to be bound, in the initial stages of thickening, into large, high-density aggregates, which may sediment more rapidly with lower intra-aggregate water content. Quantitative cryo-SEM image analysis shows that the structure of aggregates formed before flocculant addition has a determinative effect on these outcomes. Without flocculant addition, 3 stages occur in the mechanism of primary dewatering of kaolinite at pH 8: initially, the dispersed structures already show edge-edge (EE) and edge-face (EF) inter-particle associations but these are open, loose and easily disrupted; in the hindered settling region, aggregates are in adherent, chain-like structures of EE and stairstep face-face (FF) associations; this network structure slowly partially rearranges from EE chains to more compact face-face (FF) contacts densifying the aggregates with increased settling rates. During settling, the sponge-like network structure with EE and FF string-like aggregates, limits dewatering because the steric effects in the resulting partially-gelled aggregate structures are dominant. With flocculant addition, the internal structure and networking of the pre-aggregates is largely preserved but they are rapidly and effectively bound together by the aggregate-bridging action of the flocculant. The effects of initial pH and Ca ion addition on these structures are also analyzed. Statistical analysis from cryo-SEM imaging shows that there is an inverse correlation of intra-aggregate porosity with Darcian inter-aggregate permeability whereas there is a strong positive correlation of Darcian permeability with settling and primary dewatering rate as a function of pH in suspension. Graphs of partial void contributions also suggest that it is not total porosity that dominates permeability in these systems but the abundance of larger intra-aggregate voids. | 18,834,991 |
A 3-O-methylated mannogalactan from Pleurotus pulmonarius: structure and antinociceptive effect. | A polysaccharide (Mw 2.39x10(4)g/mol) was extracted with cold water from the basidiomycete Pleurotus pulmonarius, and its antinociceptive and anti-inflammatory properties were evaluated. It was a mannogalactan (MG), whose structure was characterized using mono- and two-dimensional NMR spectroscopy, methylation analysis, and a controlled Smith degradation. It had a main chain of (1-->6)-linked alpha-D-galactopyranosyl and 3-O-methyl-alpha-D-galactopyranosyl units, both of which are partially substituted at O-2 by beta-D-mannopyranosyl non-reducing ends. The MG was tested for its effects on the acetic acid-induced writhing reaction in mice, a typical model for inflammatory pain, causing a marked and dose-dependent inhibition of the nociceptive response, with ID50 of 16.2 (14.7-17.7)mg/kg and inhibition of 93+/-3% at a dose of 30mg/kg. An inflammatory response was not inhibited. | 18,834,999 |
New Uintan primates from Texas and their implications for North American patterns of species richness during the Eocene. | New omomyid fossils from the Purple Bench locality of the Devil's Graveyard Formation, middle Eocene (Uintan) of southwest Texas, are described. One specimen represents a new genus and species, herein named Diablomomys dalquesti. This new species is allocated to the tribe Omomyini, sister taxon to Omomys and Chumashius. A second specimen represents a range extension of the Utah species Mytonius hopsoni to the Trans-Pecos region of Texas. Previously, only one omomyid species (Omomys carteri) had been documented from Purple Bench and other late Uintan localities in the Devil's Graveyard Formation. These new omomyid fossils are of particular significance because Purple Bench is stratigraphically intermediate between the older late Bridgerian/early Uintan localities and the younger Duchesnean localities of Trans-Pecos Texas. With a more southerly location in the continental United States, the Devil's Graveyard Formation amplifies our understanding of patterns of North American primate richness at a time when the higher-latitude sites of the western interior were undergoing significant climatic cooling and increases in seasonality with commensurate faunal reorganization. Although the Uintan (approximately 46.5-40Ma) was a time in which anaptomorphine richness decreased dramatically, the results of this analysis suggest that Uintan omomyine richness is higher than was previously appreciated, particularly at lower latitudes. | 18,835,008 |
Identification of white adipocyte progenitor cells in vivo. | The increased white adipose tissue (WAT) mass associated with obesity is the result of both hyperplasia and hypertrophy of adipocytes. However, the mechanisms controlling adipocyte number are unknown in part because the identity of the physiological adipocyte progenitor cells has not been defined in vivo. In this report, we employ a variety of approaches, including a noninvasive assay for following fat mass reconstitution in vivo, to identify a subpopulation of early adipocyte progenitor cells (Lin(-):CD29(+):CD34(+):Sca-1(+):CD24(+)) resident in adult WAT. When injected into the residual fat pads of A-Zip lipodystrophic mice, these cells reconstitute a normal WAT depot and rescue the diabetic phenotype that develops in these animals. This report provides the identification of an undifferentiated adipocyte precursor subpopulation resident within the adipose tissue stroma that is capable of proliferating and differentiating into an adipose depot in vivo. | 18,835,024 |
Tolcapone in elderly patients with Parkinson's disease: a prospective open-label multicenter non-interventional trial. | Safety and efficacy of tolcapone was studied in 237 patients with advanced Parkinson's disease (PD) in a prospective, open-label, multicenter, non-interventional trial. Main outcome measures were tolerability (adverse events=AE) and safety parameters (liver enzymes). A subgroup analysis was performed for patients at < 70 years and > or = 70 years of age. Improvement of symptoms based on investigator global assessment was reported in 84% of all patients: 14.8% greatly improved, 42.6% improved, and 27% slightly improved. Slight worsening was reported in only 2.6% of subjects. There were no significant differences concerning the treatment efficacy between the age subgroups (p=0.74). The incidence of AE was slightly higher in the subgroup of patients > or = 70 years than in the subgroup of patients < 70 years (relative risk, RR=3.03; 95% confidence interval, CI=1.04-8.96; p=0.03), but AE judged as potentially related to tolcapone were equally distributed among both groups (8.5% vs. 2.9%, RR: 2.91; CI=0.82-10.27; p=0.08). Diarrhea was the most common potentially tolcapone-related AE in both groups. Elevations of liver enzymes (aspartate aminotransferase=AST, and alanine aminotransferase=ALT) above the upper limit of normal were observed in 19% (CI=8.3-23.4) of all patients with slightly but not statistically significant higher percentages in the young patients group compared to older patient group (RR=0.54; CI=0.28-1.04; p=0.06). This observational study provides evidence that tolcapone can be effectively and safely used for the treatment of response fluctuations in elderly patients with PD. | 18,835,049 |
Cutaneous T-cell lymphoma and Staphylococcus aureus colonization. | Bacterial infections are a common complication of cutaneous T-cell lymphoma (CTCL). The most common pathogen of cutaneous infections in CTCL patients is Staphylococcus aureus. The purpose of this study was to assess S aureus colonization rates among CTCL subjects compared to control subjects. Fifty subjects with CTCL, 25 psoriasis control subjects, and 25 healthy control subjects were included in this study. Culture swabs were obtained from nares and lesional skin or normal skin in the healthy controls. S aureus colonization rates were 44% in CTCL subjects, 48% in psoriasis subjects, and 28% in healthy control subjects (P = .29). The sample size was small, and the exclusion criteria resulted in an underestimation of the colonization rate. There was a trend for higher methicillin-sensitive S aureus colonization in the CTCL group compared with healthy control subjects. S aureus colonization may be directly related to body surface area of CTCL. | 18,835,065 |
Ferritin for the clinician. | Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage. | 18,835,072 |
The neural basis of smooth pursuit eye movements in the rhesus monkey brain. | Smooth pursuit eye movements are performed in order to prevent retinal image blur of a moving object. Rhesus monkeys are able to perform smooth pursuit eye movements quite similar as humans, even if the pursuit target does not consist in a simple moving dot. Therefore, the study of the neuronal responses as well as the consequences of micro-stimulation and lesions in trained monkeys performing smooth pursuit is a powerful approach to understand the human pursuit system. The processing of visual motion is achieved in the primary visual cortex and the middle temporal area. Further processing including the combination of retinal image motion signals with extra-retinal signals such as the ongoing eye and head movement occurs in subsequent cortical areas as the medial superior temporal area, the ventral intraparietal area and the frontal and supplementary eye field. The frontal eye field especially contributes anticipatory signals which have a substantial influence on the execution of smooth pursuit. All these cortical areas send information to the pontine nuclei, which in turn provide the input to the cerebellum. The cerebellum contains two pursuit representations: in the paraflocculus/flocculus region and in the posterior vermis. While the first representation is most likely involved in the coordination of pursuit and the vestibular-ocular reflex, the latter is involved in the precise adjustments of the eye movements such as adaptation of pursuit initiation. The output of the cerebellum is directed to the moto-neurons of the extra-ocular muscles in the brainstem. | 18,835,077 |
A model and experimental study for dissolution efficiency of gaseous substrates through in situ sparging. | Delivering electron acceptors, electron donors, and nutrients in gas state has been practiced for in situ bioremediation. A mathematical model based on air-channel concept was developed in this paper to assess the dissolution transient behavior of gaseous substrates for an in situ sparging process using their chemical and physical properties, aquifer-media characteristics, and field operating conditions. Using toluene as an example, the model was verified with experimental data obtained at field sparging rates ranging from 40 to 80Lair/min. The verified model is a useful means of predicting the dissolution behavior of gaseous substrates during sparging in an unconfined aquifer. | 18,835,090 |
Gas-liquid hybrid discharge-induced degradation of diuron in aqueous solution. | Degradation of diuron in aqueous solution by gas-liquid hybrid discharge was investigated for the first time. The effect of output power intensity, pH value, Fe(2+) concentration, Cu(2+) concentration, initial conductivity and air flow rate on the degradation efficiency of diuron was examined. The results showed that the degradation efficiency of diuron increased with increasing output power intensity and increased with decreasing pH values. In the presence of Fe(2+), the degradation efficiency of diuron increased with increasing Fe(2+) concentration. The degradation efficiency of diuron was decreased during the first 4 min and increased during the last 10 min with adding of Cu(2+). Decreasing the initial conductivity and increasing the air flow rate were favorable for the degradation of diuron. Degradation of diuron by gas-liquid hybrid discharge fitted first-order kinetics. The pH value of the solution decreased during the reaction process. Total organic carbon removal rate increased in the presence of Fe(2+) or Cu(2+). The generated Cl(-1), NH(4)(+), NO(3)(-), oxalic acid, acetic acid and formic acid during the degradation process were also detected. Based on the detected Cl(-1) and other intermediates, a possible degradation pathway of diuron was proposed. | 18,835,096 |
Nitric oxide removal from flue gas with a biotrickling filter using Pseudomonas putida. | The development of an effective biotrickling filter (BF) system to inoculate a newly isolated strain of Pseudomonas putida SB1 for the effective treatment of nitric oxide (NO) is described. The experiments were carried out in a bench-scale BF under high concentrations of O(2) and NO in simulated flue gas. A method including alternating aeration in screening and rescreening based on the pH changes for cultivating natural aerobic denitrifying bacteria was employed. The SB1 showed a denitrifying capability of 95% nitrate removal rate over a 24h period in an aerobic environment, with no nitrite accumulation. The BF system was able to consistently remove 82.9-94.2% NO when the inlet NO was 400ppm in an enriched oxygen stream of 2-20%. The oxygen had no negative effect on the aerobic denitrifier SB1, but rather enhanced the total efficiency in part by chemical oxidation and in part by the strain activities. A kinetic relation between the oxygen concentration and biological NO removal was developed to confirm that the microbial metabolism played the main role. 79.3% of the total NO removal can be attributed to bio-denitrifying at 20% oxygen, and most chemical oxidation occurred concurrently. Overall, the study demonstrates that NO removal by the aerobic denitrifying process in BF is feasible in flue gas. | 18,835,098 |
Magnetic resonance imaging of renal involvement in genetically studied patients with tuberous sclerosis complex. | To evaluate renal involvement in tuberous sclerosis complex (TSC). A series of 24 TSC patients (19 with genetically demonstrated disease), underwent abdominal 1.0-T MR imaging with axial/coronal T1- and T2-weighted scans, with/without fat saturation. We looked for angiomyolipomas (AMLs) and cysts in 47 kidneys of 24 patients. We evaluated the percentage of parenchymal involvement by manual contouring on the coronal scans in 39 kidneys of 20 patients. We detected AMLs in 15/24 (63%) patients and in 27/47 (57%) kidneys, cysts in 14/24 (58%) and in 26/47 (55%); respectively. AMLs were found in 2/4 TSC1 and in 11/15 TSC2 patients, cysts were found in 2/4 TSC1 and in 9/15 TSC2 patients. The global renal involvement ranged from 0 to 32% (median, 18%) in TSC1 and from 0 to 100% (median, 39%) in TSC2 patients. A fair correlation (r=.464) was found between patient's age and renal involvement, a good correlation (r=0.655) between renal involvement and creatinine clearance. Renal parenchyma of TSC patients can be evaluated with MR imaging. A detectable renal involvement was found in 83% of patients, higher in TSC2 than in TSC1. Renal function seems to correlate with renal involvement quantified with MR imaging. | 18,835,118 |
Preserved awareness of their cognitive deficits in patients with schizophrenia: convergent validity of the SSTICS. | This study aimed to examine the convergent validity of the SSTICS. The association between the SSTICS and the five-factor model of the PANSS was also examined. One hundred and seventy-six schizophrenia-spectrum disorder patients were recruited. A correlation analysis was performed. The SSTICS score correlated with the score on the FPSES. The SSTICS score also correlated with the cognition factor of the PANSS. Our results demonstrate that the SSTICS is a good instrument for evaluating the subjective complaints of patients with schizophrenia. They also reveal good concordance between cognitive impairments experienced by patients and cognitive disorders assessed by a clinical rater. | 18,835,134 |
Pharmacodynamic activity of the lantibiotic MU1140. | This study evaluated the pharmacodynamics of the lantibiotic MU1140 and the ability of selected organisms to develop resistance to this antibiotic. MU1140 demonstrated activity against all Gram-positive organisms tested, including oxacillin- and vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis (VREF). No activity was observed against Gram-negative bacteria or yeast. Time-kill studies revealed that MU1140 was rapidly bactericidal against Streptococcus pneumoniae and multidrug-resistant S. aureus, whilst it was bacteriostatic against VREF. In vitro resistance development to MU1140, tested by sequential subculturing in subinhibitory concentrations of MU1140, revealed a stable threefold increase in the minimum inhibitory concentration (MIC) for S. aureus and S. pneumoniae. Subsequent subculturing of the strains with elevated MICs in antibiotic-free media for 7 days did not result in a reduction of their MIC values for MU1140. Collectively, our findings illustrate the therapeutic potential of MU1140 for management of Gram-positive infections. | 18,835,136 |
Suicidal ideation and time perspective in high school students. | Many studies have enlightened the relevance of deepening our knowledge of suicidal ideation among adolescents. However, research has given insufficient attention to the impact of time perspective on suicidal ideation: the present study confirms this relationship in a large sample of adolescents. A survey was conducted on a sample of 3700 Italian adolescents. We obtained data using a structured questionnaire addressing suicidal ideation, mental health status, self-esteem, individual and family characteristics, and time perspective (ZTPI) in three temporal frames: the past, present and future, and the attitude related to each one of them. Data were analyzed using bivariate and multivariate analyses. Overall, 9.2% of the sample reported severe suicidal ideation during the past two weeks; 7.6% reported moderate suicidal ideation. Female adolescents were more likely to report severe suicidal ideation when compared to males (chi((2))(2)=13.38, P=.001). There were no differences regarding age (chi((1))(2)=2.81, P=.245) and SES (chi((2))(2)=8.67, P=.08). The first discriminant function was mostly explained by psychopathological symptoms (General Global Index), self-esteem and two dimensions of the ZTPI (Negative Past and Fatalistic Present). Differences in time perspective dimensions between moderate and severe ideators suggest that these groups should be considered and analyzed as two discrete groups in further research. | 18,835,138 |
Copper and boron fixation in wood by pyrolytic resins. | A phenol-formaldehyde (PF)-resin designed to penetrate wood and immobilize copper and boron in wood cells for protection against decay was investigated. The phenol portion of the PF-resin was partially substituted with pyrolysis oil derived from softwood bark. The objective was to reduce the environmental impact associated with the production of petroleum-borne phenol, as well as to improve the product economics. Leaching tests were conducted with three different formulas of resins containing 50%, 75% or 85% by weight of pyrolytic oil on a total phenol basis. The leachates were analyzed for the presence of copper by atomic absorption spectroscopy while inductively coupled plasma spectroscopy was used for boron detection. Copper leaching was reduced up to 18 times when comparing the treatments with and without the resin. Preservative leaching varied between wood species as well as between the resins containing different concentrations of pyrolytic oil. The organic leachates were measured using gas chromatography and mass spectroscopy. Trace amounts of organics, mostly acetic acid, were found in the leachates. | 18,835,155 |
NODAPA-OH and NODAPA-(NCS)n: synthesis, 68Ga-radiolabelling and in vitro characterisation of novel versatile bifunctional chelators for molecular imaging. | This report concerns synthesis, (68)Ga-radiolabelling and stability data of 1,4,7-triazacyclononane-1,4-diacetic acid-7-p-isothio-cyanatophenyl-acetic acid (NODAPA-NCS), 1,4,7-triazacyclononane-1-acetic acid-4,7-di-p-isothiocyanatophenyl-acetic acid (NODAPA-(NCS)(2)) and 1,4,7-triazacyclononane-1,4-diacetic acid-7-p-hydroxyphenyl-acetic acid (NODAPA-OH), versatile bifunctional chelators with potential for molecular imaging. Protein binding and exemplified conjugation are also reported. | 18,835,159 |
Quantitative structure-activity relationship studies on 1-aryl-tetrahydroisoquinoline analogs as active anti-HIV agents. | Predictive quantitative structure-activity relationship analysis was developed for a diverse series of recently synthesized 1-aryl-tetrahydroisoquinoline analogs with anti-HIV activities in this study. The conventional 2D-QSAR models were developed by genetic function approximation (GFA) and stepwise multiple linear regression (MLR) with acceptable explanation of 94.9% and 95.5% and good predicted power of 91.7% and 91.7%, respectively. The results of the 2D-QSAR models were further compared with 3D-QSAR model generated by molecular field analysis (MFA), investigating the substitutional requirements for the favorable receptor-drug interaction and quantitatively indicating the important regions of molecules for their activities. The results obtained by combining these methodologies give insights into the key features for designing more potent analogs against HIV. | 18,835,162 |
Non-infective morbidity in diabetic patients undergoing coronary and heart valve surgery. | Studies of postoperative morbidity in diabetics have focussed on infection; however, autonomic and cardiovascular complications of diabetes potentially increase the risk for non-infective morbidity. We sought to investigate major non-infective early postoperative complications in diabetic patients. We identified diabetics who underwent CABG and/or valve operation from 1998 through 2007, and compared their clinical characteristics and outcome with a contemporaneous cohort of non-diabetic patients. The demographic characteristics of 1145 diabetics were similar to 5534 non-diabetic patients (mean age 66+/-9 years vs 66+/-10 years, p=0.45, female 27.5% vs 26.7%, p=0.59, respectively). Class III/IV angina symptoms (43.9% vs 34.9%, p<0.0001), intravenous nitrates therapy (10.4% vs 6.6%, p<0.0001), heart failure (24.8% vs 20.4%, p=0.001), prior myocardial infarction (37% vs 31%, p<0.0001), ejection fraction </=0.50 (34.5% vs 23.0%, p<0.0001), triple vessel disease (66.3% vs 54.8%, p<0.0001), renal insufficiency (3.6% vs 1.5%, p<0.0001) and peripheral vascular disease (16.1% vs 8.7%) were prevalent amongst diabetics. The predominant operation was CABG (diabetic 84.8% vs non-diabetic 73.9%). Low cardiac output (28.3% vs 24.0%, p=0.002), renal dialysis (2.0% vs 0.8%, p<0.0001) and cerebrovascular events (5.1% vs 3.8%, p=0.04) more often complicated recovery of diabetic patients, but operative mortality was similar for both groups. However, postoperative myocardial infarction was less common in diabetics (0.5% vs 1.4%, p=0.02). Diabetes was not a risk factor for the composite endpoint of major non-infective morbidity and operative mortality (OR 1.15, 95% CI 0.97-1.37, p=0.10). Diabetic patients were prone to longer postoperative hospitalisation (9.7+/-10.5 days vs 8.4+/-6.7 days, p<0.0001) and discharge to a convalescence facilities (9.8% vs 6.9%, p<0.0001). Diabetic patients present for surgery with higher prevalence of cardiovascular risk factors and are more likely to develop major non-infective complications, including cardiac, renal and neurological dysfunction, even though diabetes does not directly influence non-infective postoperative morbidity following CABG and/or valve operations. | 18,835,187 |
Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis. | Fas is highly expressed in activated and germinal center (GC) B cells but can potentially be inactivated by misguided somatic hypermutation. We employed conditional Fas-deficient mice to investigate the physiological functions of Fas in various B cell subsets. B cell-specific Fas-deficient mice developed fatal lymphoproliferation due to activation of B cells and T cells. Ablation of Fas specifically in GC B cells reproduced the phenotype, indicating that the lymphoproliferation initiates in the GC environment. B cell-specific Fas-deficient mice also showed an accumulation of IgG1(+) memory B cells expressing high amounts of CD80 and the expansion of CD28-expressing CD4(+) Th cells. Blocking T cell-B cell interaction and GC formation completely prevented the fatal lymphoproliferation. Thus, Fas-mediated selection of GC B cells and the resulting memory B cell compartment is essential for maintaining the homeostasis of both T and B lymphocytes. | 18,835,195 |
Association of increased tracheal mucus accumulation with poor willingness to perform in show-jumpers and dressage horses. | The objective of this study was to examine the association of pharyngeal lymphoid hyperplasia (PLH), recurrent laryngeal neuropathy (RLN), mucus accumulation (MA) score and tracheobronchial secretion neutrophil percentage (TBS-N) with rider-assessed performance in sport horses. Airway endoscopy scores, tracheobronchial secretion cytology, rider-assessed general impression and willingness to perform were investigated in 171 top-level sport horses. Increased MA appears to be associated with poor willingness to perform in sport horses. Older horses had decreased PLH scores and increased TBS-N. Mucus accumulation scores > or =3 were associated with increased odds (mean 9.92; upper and lower 95% confidence intervals: 1.5-64.6) of poor rather than excellent willingness to perform. A TBS-N of 20-50% compared with <20% was associated with decreased odds (median 0.11; upper and lower 95% CI: 0.02-0.66) of poor rather than excellent willingness to perform. In addition, horses with an RLN grade > or =2 had significantly higher odds for giving a poorer general impression and willingness to perform. This finding, however, must be interpreted with caution, since only two horses had significant RLN (grade > or =3). | 18,835,198 |
Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block. | Effector memory T (Tem) cells are essential mediators of autoimmune disease and delayed-type hypersensitivity (DTH), a convenient model for two-photon imaging of Tem cell participation in an inflammatory response. Shortly (3 hr) after entry into antigen-primed ear tissue, Tem cells stably attached to antigen-bearing antigen-presenting cells (APCs). After 24 hr, enlarged Tem cells were highly motile along collagen fibers and continued to migrate rapidly for 18 hr. Tem cells rely on voltage-gated Kv1.3 potassium channels to regulate calcium signaling. ShK-186, a specific Kv1.3 blocker, inhibited DTH and suppressed Tem cell enlargement and motility in inflamed tissue but had no effect on homing to or motility in lymph nodes of naive and central memory T (Tcm) cells. ShK-186 effectively treated disease in a rat model of multiple sclerosis. These results demonstrate a requirement for Kv1.3 channels in Tem cells during an inflammatory immune response in peripheral tissues. Targeting Kv1.3 allows for effector memory responses to be suppressed while central memory responses remain intact. | 18,835,197 |
Effects of intermittent high-intensity exercise and carbohydrate supplementation on IGF-1 and glycogen of Wistar rats. | The aim of this study was to analyze the association between glucose infusion during intermittent physical exercise and its metabolic effects on rats. Forty male rats were divided into eight groups based on training (intermittent), exercise and carbohydrate intake (glucose 20%): TEC (trained exercised with carbohydrate), TES (trained exercised without carbohydrate), TNC (trained non-exercised with carbohydrate), TNS (trained non-exercised without carbohydrate), UEC (untrained exercised with carbohydrate), UES (untrained exercised without carbohydrate), UNC (untrained non-exercised with carbohydrate) and UNS (untrained non-exercised without carbohydrate). The training and/or exercise protocol consisted of the rats running on a treadmill for 1 min above the lactate threshold, or running below the lactate threshold for 30s, intermittently for 30 min. Blood was analyzed for glycemia, lactate and IGF-1. Muscle and liver glycogen were measured (T2). Glycemia was found to be different in T2 compared to T1 in the TEC, TNC, UEC and UNC groups. Lactate was higher in T2 than in T1, but remained within the lactate threshold. Glycogen showed higher concentrations in the trained groups and, whether trained or not, in the supplemented groups. IGF-1 levels were higher in exercised rats independent of supplementation or glycogen levels. Trained rats showed lower IGF-1 when exercising than did the untrained animals. We conclude that intermittent exercise is beneficial in preventing a trained lactate pool, and that, in association with glucose supplementation, intermittent exercise will be efficient both in preventing a trained lactate pool and in maintaining sufficient glycemia levels. Exercise raises IGF-1 levels, whereas training inverts this relationship. | 18,835,207 |
Challenges to effective crisis management: using information and communication technologies to coordinate emergency medical services and emergency department teams. | The purpose of this study is to identify the major challenges to coordination between emergency department (ED) teams and emergency medical services (EMS) teams. We conducted a series of focus groups involving both ED and EMS team members using a crisis scenario as the basis of the focus group discussion. We also collected organizational workflow data. We identified three major challenges to coordination between ED and EMS teams including ineffectiveness of current information and communication technologies, lack of common ground, and breakdowns in information flow. The three challenges highlight the importance of designing systems from socio-technical perspective. In particular, these inter-team coordination systems must support socio-technical issues such as awareness, context, and workflow between the two teams. | 18,835,211 |
Quantitative analysis of the effect of porosity on the fatigue strength of bone cement. | This paper reports on the effects of porosity and its distribution on the fatigue strength of bone cement. Hand-mixed (HM) and vacuum-mixed (VM) bone cement samples were fatigue tested to failure. The point of failure commonly coincided with large single pores (in the VM materials) and multiple pores in clusters (in the HM material). The effect of pores was analysed using the Theory of Critical Distances (TCD), a theory previously developed to explain the effect of notches and other stress concentrations on fatigue and fracture. Clusters of pores were analysed by developing a criterion to decide whether local cracking would act to link pores together, forming a single stress concentration of more complex shape. This approach enabled us to predict the high-cycle fatigue strength of samples containing clusters of pores, with good accuracy (errors less than 13%). We then used the analysis to develop general rules for the effect of pore size and proximity on fatigue strength. For example, we showed that a single pore of 2mm diameter or more would cause a significant decrease in the fatigue strength (compared to that of pore-free material); however, two pores of only 1mm diameter in close proximity would be equally damaging. This demonstrates the importance not only of pore size but also of pore density and distribution. However, pores do have beneficial effects such as improved drug dispersion, bone ingrowth and crack tip blunting. Therefore, given the findings from this study, a possible step forward in the development of surgical bone cements may involve a compromise in which relatively small pores are evenly distributed throughout the material. | 18,835,229 |
Management of the upper airway and congenital cystic lung diseases in neonates. | Congenital upper airway obstruction can pose difficult problems immediately after birth. Newer strategies to maintain the airway in such situations include pharyngeal ventilation, the laryngeal mask airway and flexible fibreoptic intubation. These methods have decreased the potential for malformations such as Pierre Robin sequence to cause perinatal hypoxia. The most devastating upper airway problem is total obstruction at the supraglottic, glottic or tracheal level without tracheo-oesophageal communication. This can usually be detected prenatally and its management may include the use of the EXIT (ex-utero intrapartum) procedure. Congenital space-occupying lesions of the lung can be detected prenatally with ultrasound. Their management must be individualised, as their pre- and postnatal development is difficult to predict. Very large lesions can lead to lung hypoplasia or fetal hydrops. Management may include prenatal surgery, shunting and, rarely, an EXIT procedure during birth. A few children may require extracorporeal membrane oxygenation postnatally. | 18,835,231 |
Applicability of multigene family-specific antibodies toward studies of the subtilases in Arabidopsis thaliana. | Polyclonal antibodies were made to two synthetic peptides with sequences patterned after conserved regions in a multigene family of 56 subtilisin-related proteolytic enzymes in Arabidopsis thaliana. GST-fusion proteins encompassing full-length or partial cDNAs bearing putative epitope regions were cloned and expressed in Escherichia coli. Immunoblots showed that the antibodies bound 12 of 13 fusion proteins tested. About 27 more subtilase genes code for regions with sequences very similar to the epitope regions of the subtilases that were visualized on the immunoblots. Subtilases in rosette and cauline leaves, stems, flowers, and siliques could be distinguished by the antibodies; some binding the two antibodies to similar extents, while others bind preferentially or almost exclusively to one or the other antibody. When antibodies were used to monitor ion-exchange fractionation of seedling extracts, one specific subtilase was identified by LC-MS-MS. The specificity of the antibodies extended to subtilases in soybean. These studies show that multigene family-specific antibodies can be applied to the study of gene families, where sequence similarities make it difficult to produce antibodies specific for each individual protein in the group. | 18,835,234 |
Large-scale expression, purification, and characterization of an engineered prostacyclin-synthesizing enzyme with therapeutic potential. | Recently, we reported that a novel hybrid enzyme (TriCat enzyme), engineered by linking human cyclooxygenase-2 (COX-2) with prostacyclin (PGI(2)) synthase (PGIS) together through a transmembrane domain, was able to directly integrate the triple catalytic (TripCat) functions of COX-2 and PGIS and effectively convert arachidonic acid (AA) into the vascular protector, PGI(2) [K.H. Ruan, H. Deng, S.P. So, Biochemistry 45 (2006) 14003-14011]. In order to confirm the important biological activity and evaluate its therapeutic potential, it is critical to characterize the properties of the enzyme using the purified protein. The TriCat enzyme cDNA was subcloned into a baculovirus vector and its protein was expressed in Sf-9 cells in large-scale with a high-yield ( approximately 4% of the total membrane protein), as confirmed by Western blot and protein staining. The Sf-9 cells' membrane fraction, rich in TriCat enzyme, exhibited strong TriCat functions (K(m)=3 microM and K(cat)=100 molecules/min) for the TriCat enzyme and was 3-folds faster in converting AA to PGI(2) than the combination of the individual COX-2 and PGIS. Another superiority of the TriCat enzyme is its dual effect on platelet aggregation: it completely inhibited platelet aggregation at the low concentration of 2 microg/ml and then displayed the ability to reverse the initially aggregated platelets to their non-aggregated state. Furthermore, multiple substrate-binding sites were confirmed in the single protein by high-resolution NMR spectroscopy, using partially purified TriCat enzyme. These studies have clearly demonstrated that the isolated TriCat enzyme protein functions in the selective biosynthesis of the vascular protector, PGI(2), and revealed its potential for anti-thrombosis therapeutics. | 18,835,243 |
Reduced expression of SRC family kinases decreases PI3K activity in NBS1-/- lymphoblasts. | SRC family kinases (SFKs) are involved in the activation of phosphatidylinositol-3-kinase (PI3K). In addition, the activity of this lipid kinase can be regulated by the DNA repair protein NBS1. Here, we describe a disturbed expression of some members of the non-receptor tyrosine kinase family in lymphoblastoid cell lines generated from cells of Nijmegen breakage syndrome (NBS) patients. Especially, only minor amounts of the kinases LCK and HCK are expressed in the NBS1(-/-) cell lines as compared to the consanguineous NBS1(+/-) cells. We demonstrate that SFK activity is important for a proper activation of PI3K in these cells and that it is reduced in NBS1(-/-) cells. We provide evidence that the observed reduced PI3K activity in NBS lymphoblasts is caused by an impaired expression of the SFKs LCK and/or HCK. Thus, our data establish a new function for the NBS1 protein as a regulator of PI3K activity via SFK members. | 18,835,245 |
The stigmatization of obesity in children. A survey in Greek elementary schools. | This study investigates elementary school children's prejudice towards obesity. A sample of 1861 underweight, normal, overweight and obese children from Central Greece were instructed to rank 6 drawings of same sex children with various physical disabilities, obesity or no disability at all ("healthy"), according to how much they liked each child. Results showed that all participants ranked the obese child last, showing that even obese individuals show negative attitudes towards obesity. Gender differences were recorded in almost all the drawings. Girls liked obese children and those with facial disfigurement less than boys did while boys disliked children with physical disabilities more than girls. | 18,835,307 |
Induction of antibody response against hepatitis E virus (HEV) with recombinant human papillomavirus pseudoviruses expressing truncated HEV capsid proteins in mice. | A hepatitis E virus (HEV) vaccine would be valuable to reduce the morbidity and mortality associated with the infection in endemic areas. HEV pseudocapsids and epidermal delivery of HEV ORF2 DNA vaccine by gene-gun have been shown to confer protection against virus challenge in monkeys. Vectorization of a DNA vaccine by virus-like particles is a new immunization approach. We report here the successful immunization of mice with two ORF2 genes encapsidated into human papillomavirus type 31 virus-like particles. The HEV genes ORF2(112-660) and ORF2(112-608) were optimized for expression in mammalian cells and inserted in a baculovirus-derived vector for expression in insect cells. When expressed in Sf21 insect cells, ORF2(112-660) led to the production of irregular 15 nm particles that accumulated in the cytoplasm of the cells, whereas ORF2(112-608) induced the production of 18nm particles that were present in both the cell culture medium and the cell cytoplasm. Anti-HEV immune responses were higher for the 15 nm particles (HEV112-660) than that for to the 18 nm particles (HEV112-608). Delivery into mice of two HEV ORF2 genes via a papillomavirus VLP was very effective in the induction of anti-HEV antibodies. In addition, an effective immune response to human papillomavirus capsids occurred. These engineered pseudoviruses were thus demonstrated to induce immune responses to both hepatitis E virus and human papillomavirus when they were administered to mice intramuscularly. | 18,835,319 |
MG-132 inhibits the TCDD-mediated induction of Cyp1a1 at the catalytic activity but not the mRNA or protein levels in Hepa 1c1c7 cells. | Previous studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced degradation of aryl hydrocarbon receptor (AhR) is inhibited by MG-132, a potent inhibitor of the 26S proteasome. Therefore, the current study aims to address the effect of MG-132 on the AhR-regulated gene, cytochrome P450 1a1 (Cyp1a1), using murine hepatoma Hepa 1c1c7 cells. Our results showed that MG-132 at the highest concentration tested, 10 microM significantly increased the Cyp1a1 at mRNA, protein and catalytic activity levels through a transcriptional mechanism. On the other hand, MG-132 further potentiated the TCDD-mediated induction of Cyp1a1 at mRNA but not at protein level. In contrast, MG-132 significantly inhibited the TCDD-mediated induction of Cyp1a1 catalytic activity. In addition, we showed that the decrease in Cyp1a1 catalytic activity is not Cyp specific, as MG-132 significantly inhibited Cyp2b1 and total cytochrome P450 catalytic activities. These results prompted us to examine the effect of MG-132 on total cellular heme content and heme oxygenase-1 (HO-1) mRNA, a rate limiting enzyme of heme degradation. Our results showed that MG-132 significantly induced HO-1 mRNA in a concentration-dependent manner. Furthermore, MG-132 potentiated the induction of HO-1 mRNA by TCDD in a concentration-dependent manner. The induction of HO-1 mRNA level coincided with a decrease in total cellular heme content. In conclusion, the present study demonstrates for the first time that MG-132, despite of increasing Cyp1a1 mRNA expression, it decreases its activity probably through decreasing its heme content. | 18,835,339 |
Preparation of polysaccharide glassy microparticles with stabilization of proteins. | This study investigates a method of preparing hazard-resistant protein-loaded polysaccharide glassy microparticles using freezing-induced phase separation method without exposure to water/oil, water/air interface and cross-linking reagents. Model protein (such as bovine serum albumin, myoglobin and beta-galactosidase (beta-Gal)) was dissolved in water together with dextran and polyethylene glycol (PEG), followed by a freezing process to form a temperature-stabilized aqueous-aqueous emulsion wherein dextran separated out as the dispersed phase with protein partitioned in preferentially. The frozen sample was freeze-dried and washed with dichloromethane (DCM) to remove the PEG continuous phase, after which protein-loaded polysaccharide particles, 1-4 microm in diameter, were harvested. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) patterns showed that the particles were in glassy state. These glassy polysaccharide microparticles can well protect the delicate structure of proteins and preserve their bioactivities under deleterious environment interacting with organic solvents, vortex and centrifugation processes that often involve during the formulation processes leading to polymer-based sustained-release systems. Therefore, this freezing-induced phase separation method is a mild and effective way to encapsulate protein into hazard-resistant polysaccharide glassy particles, which ensure its stability in subsequent formulating processes that leads to polymer-based sustained-release system. | 18,835,346 |
Trace amounts of copper exacerbate beta amyloid-induced neurotoxicity in the cholesterol-fed mice through TNF-mediated inflammatory pathway. | Evidence has been gathered to suggest that trace amounts of copper induce neurotoxicity by interaction with elevated cholesterol in diet. Step-through task and Morris water maze task were used to evaluate cognitive function in the animals. Although a 16-week copper treatment alone in mice showed no significant change in learning and memory performances, cholesterol treatment significantly induced learning and memory impairments, which could be exacerbated by the co-treatment with copper. Immunohistochemical studies revealed that trace amounts of copper further stimulated the amyloid precursor protein (APP) upregulation and contributed to amyloid beta-peptide (Abeta) deposition in the brain of cholesterol-fed mice. Western blot analysis showed that copper also increased the protein expression levels of tumor necrosis factor-alpha (TNF-alpha) and the degradation of IkappaB proteins in the brain of cholesterol-fed mice. Furthermore, increased production of high inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expressions were detected in the hippocampus and cerebral cortex of copper and cholesterol co-treated mice by immunohistochemical analysis. These findings suggest that trace amounts of copper could induce APP upregulation, activate inflammatory pathway and exacerbate neurotoxicity in cholesterol-fed mice. | 18,835,350 |
Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney. | The mammalian metanephric kidney is derived from the intermediate mesoderm. In this report, we use molecular fate mapping to demonstrate that the majority of cell types within the metanephric kidney arise from an Osr1(+) population of metanephric progenitor cells. These include the ureteric epithelium of the collecting duct network, the cap mesenchyme and its nephron epithelia derivatives, the interstitial mesenchyme, vasculature and smooth muscle. Temporal fate mapping shows a progressive restriction of Osr1(+) cell fates such that at the onset of active nephrogenesis, Osr1 activity is restricted to the Six2(+) cap mesenchyme nephron progenitors. However, low-level labeling of Osr1(+) cells suggests that the specification of interstitial mesenchyme and cap mesenchyme progenitors occurs within the Osr1(+) population prior to the onset of metanephric development. Furthermore, although Osr1(+) progenitors give rise to much of the kidney, Osr1 function is only essential for the development of the nephron progenitor compartment. These studies provide new insights into the cellular origins of metanephric kidney structures and lend support to a model where Osr1 function is limited to establishing the nephron progenitor pool. | 18,835,385 |
Protein-protein interactions and lens transparency. | Past studies have identified posttranslational modifications of human lens proteins occurring during cataract formation, and have also demonstrated that protein-protein interactions exist between different lens crystallins. Based upon current theories of lens transparency, these posttranslational modifications and their possible effects upon crystallin interactions may be the key to understanding why the lens is able to transmit light, and why transmission is decreased during cataractogenesis. This review will summarize current knowledge of posttranslational modifications during human cataractogenesis, and will propose their possible role in protein-protein interactions that are thought to be necessary for lens transparency. Based upon this premise, model systems will be described that will test the validity of the theory. | 18,835,387 |
Contribution of gustation to the palatability of linoleic acid. | We investigated the palatability of a low concentration of linoleic acid (LA) in short-term two-bottle choice tests and licking tests. To examine the contribution of gustation, mice were rendered anosmic with olfactory nerve transection surgery and test solutions were prepared using mineral oil (saturated long-chain hydrocarbon) to minimize textural effects. In the two-bottle choice tests between various pairs of different concentrations of corn oil and LA, both anosmic and the sham-operated mice constantly preferred a higher concentration of corn oil and LA. In the licking tests, the initial licking rate for 1% LA was higher than that for mineral oil in anosmic mice. In accordance with the results of the two-bottle choice test, the initial licking rate for corn oil and LA increased in a concentration-dependent manner in both anosmic and sham-operated mice in the licking test, and reached its peak at 100% corn oil and 1% LA. A preference comparison between 1% LA and 100% corn oil showed that anosmic mice preferred 1% LA over 100% corn oil. These results suggest that mice could recognize dietary fat and fatty acid solutions in the oral cavity without any olfactory or textural cues and the fatty acid recognition on their tongues might provide a pivotal cue to how dietary fat is recognized in the oral cavity. | 18,835,400 |
Development of an in vitro test battery for assessing chemical effects on bovine germ cells under the ReProTect umbrella. | Current European legislation for the registration and authorization of chemicals (REACH) will require a dramatic increase in the use of animals for reproductive toxicity testing. Since one objective of REACH is to use vertebrates only as last resort, the development and validation of alternative methods is urgently needed. For this purpose ReProTect, an integrated research project funded by the European Union, joining together 33 partners with complementary expertise in reproductive toxicology, was designed. The study presented here describes a battery of two tests developed within ReProTect. The objective of these tests is the detection of chemical effects during the processes of oocyte maturation and fertilisation in a bovine model. The corresponding toxicological endpoints are the reaching of metaphase II and the formation of the pronuclei respectively. Fifteen chemicals have been tested (Benzo[a]pyrene, Busulfan, Butylparaben, Cadmium Chloride, Carbendazim, Cycloheximide, Diethylstilbestrol, Genistein, Ionomycin, Ketoconazole, Lindane, Methylacetoacetate, Mifepristone, Nocodazole and DMSO as solvent) demonstrating high intra-laboratory reproducibility of the tests. Furthermore, the responses obtained in both tests, for several substances, had a good correlation with the available in vivo and in vitro data. These tests therefore, could predictably become part of an integrated testing strategy that combines the bovine models with additional in vitro tests, in order to predict chemical hazards on mammalian fertility. | 18,835,402 |
Evaluation of proinflammatory cytokine production and liver injury induced by plasmid DNA/cationic liposome complexes with various mixing ratios in mice. | The purpose of this study was to investigate the cytokine production and liver injury induced by lipoplexes prepared with DOTMA/cholesterol and DOTAP/cholesterol liposomes with various mixing ratios in mice. Lipoplexes were prepared with pCMV-Luc and DOTMA/cholesterol or DOTAP/cholesterol liposomes. After intravenous administration into the mice, organ luciferase activity and serum TNFalpha and ALT were measured to evaluate the transfection efficacy, cytokine production and liver injury. After intravenous administration of these lipoplexes, basically the serum TNFalpha and ALT levels were in agreement with the transfection efficacy of the lipoplexes. The cytokine production and liver injury were markedly suppressed by reducing the pDNA dose, and achieved normal levels at a pDNA dose of 0.47 mg/kg. As far as the effects of the charge ratio at this low pDNA dose are concerned, the charge ratios of the lipoplexes affected the transfection efficacy, but not the cytokine production and liver injury. After intravenous administration of either DOTAP/cholesterol or DOTMA/cholesterol liposomes, serum TNFalpha and ALT levels were normal, suggesting that liver injury as well as cytokine production was caused by lipoplexes, but not by cationic liposomes. This information will be valuable for the future optimization of the preparation conditions of lipoplexes for use in clinical gene therapy. | 18,835,442 |
AFM for analysis of structure and dynamics of DNA and protein-DNA complexes. | This paper describes protocols for studies of structure and dynamics of DNA and protein-DNA complexes with atomic force microscopy (AFM) utilizing the surface chemistry approach. The necessary specifics for the preparation of functionalized surfaces and AFM probes with the use of silanes and silatranes, including the protocols for synthesis of silatranes are provided. The methodology of studies of local and global conformations DNA with the major focus on the time-lapse imaging of DNA in aqueous solutions is illustrated by the study of dynamics of Holliday junctions including branch migration. The analysis of nucleosome dynamics is selected as an example to illustrate the application of the time-lapse AFM to studies of dynamics of protein-DNA complexes. The force spectroscopy is the modality of AFM with a great importance to various fields of biomedical studies. The AFM force spectroscopy approach for studies of specific protein-DNA complexes is illustrated by the data on analysis of dynamics of synaptic SfiI-DNA complexes. When necessary, additional specifics are added to the corresponding example. | 18,835,446 |
Characterisation of chicken Campylobacter jejuni isolates using resolution optimised single nucleotide polymorphisms and binary gene markers. | The principal objective of this study was to determine if Campylobacter jejuni genotyping methods based upon resolution optimised sets of single nucleotide polymorphisms (SNPs) and binary genetic markers were capable of identifying epidemiologically linked clusters of chicken-derived isolates. Eighty-eight C. jejuni isolates of known flaA RFLP type were included in the study. They encompassed three groups of ten isolates that were obtained at the same time and place and possessed the same flaA type. These were regarded as being epidemiologically linked. Twenty-six unlinked C. jejuni flaA type I isolates were included to test the ability of SNP and binary typing to resolve isolates that were not resolved by flaA RFLP. The remaining isolates were of different flaA types. All isolates were typed by real-time PCR interrogation of the resolution optimised sets of SNPs and binary markers. According to each typing method, the three epidemiologically linked clusters were three different clones that were well resolved from the other isolates. The 26 unlinked C. jejuni flaA type I isolates were resolved into 14 SNP-binary types, indicating that flaA typing can be unreliable for revealing epidemiological linkage. Comparison of the data with data from a fully typed set of isolates associated with human infection revealed that abundant lineages in the chicken isolates that were also found in the human isolates belonged to clonal complex (CC) -21 and CC-353, with the usually rare C-353 member ST-524 being especially abundant in the chicken collection. The chicken isolates selected to be diverse according to flaA were also diverse according to SNP and binary typing. It was observed that CC-48 was absent in the chicken isolates, despite being very common in Australian human infection isolates, indicating that this may be a major cause of human disease that is not chicken associated. | 18,835,503 |
Effect of monomeric and oligomeric sugar osmolytes on DeltaGD, the Gibbs energy of stabilization of the protein at different pH values: is the sum effect of monosaccharide individually additive in a mixture? | Thermal denaturation curves of ribonuclease-A were measured by monitoring changes in the far-UV circular dichroism (CD) spectra in the presence of different concentrations of six sugars (glucose, fructose, galactose, sucrose, raffinose and stachyose) and mixture of monosaccharide constituents of each oligosaccharide at various pH values in the range of 6.0-2.0. These measurements gave values of T(m) (midpoint of denaturation), DeltaH(m) (enthalpy change at T(m)), DeltaC(p) (constant-pressure heat capacity change) under a given solvent condition. Using these values of DeltaH(m), T(m) and DeltaC(p) in appropriate thermodynamic relations, thermodynamic parameters at 25 degrees C, namely, DeltaG(D)(o) (Gibbs energy change), DeltaH(D)(o) (enthalpy change), and DeltaS(D)(o) (entropy change) were determined at a given pH and concentration of each sugar (including its mixture of monosaccharide constituents). Our main conclusions are: (i) each sugar stabilizes the protein in terms of T(m) and DeltaG(D)(o), and this stabilization is under enthalpic control, (ii) the protein stabilization by the oligosaccharide is significantly less than that by the equimolar concentration of the constituent monosaccharides, and (iii) the stabilization by monosaccharides in a mixture is fully additive. Furthermore, measurements of the far- and near-UV CD spectra suggested that secondary and tertiary structures of protein in their native and denatured states are not perturbed on the addition of sugars. | 18,835,508 |
Prognostic factors after liver resection for hepatocellular carcinoma with hepatitis B virus-related cirrhosis: surgeon's role in survival. | Little is known in judging significant factors that affect the outcome of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV)-related cirrhosis undergoing liver resection. The aim of the present study is to investigate the controllable and uncontrollable poor prognostic factors for hepatectomy in patients with HBV-related cirrhosis. Clinical and pathological data of 412 HCC patients with HBV-related cirrhosis undergoing liver resection from October 1996 to October 2006 were retrospectively reviewed and the prognostic risk factors were analyzed by univariate and multivariate analyses. Cumulative survival was calculated with respect to the number of prognostic risk factors. The significant risk factors for decreasing both the overall and disease-free survival of patients were: (1) ascites volume of more than 500 ml; (2) prothrombin time of more than 4s; (3) serum AFP of more than 400 ng/ml; (4) tumor distribution in two lobes; (5) vascular invasion; (6) capsule absence; and (7) blood transfusion of more than 600 ml. Moreover, female gender and operation time of more than 5h are risk factors of tumor recurrence but not for the patients' overall survival. The 3-year survival rate decreased from 100% to 0 as the number of risk factors in the patients increased from zero to four or more. Patients who had two or more preoperative risk factors were poor candidates for liver resection, with a 3-year survival rate of 8.5%. The survival of HCC patients with HBV-related cirrhosis after liver resection depends on preoperative liver reserve, tumor status and blood transfusion. Tumor status cannot be altered; however, the surgeon can do a great favor to the prognosis of patients by minimizing bleeding and blood transfusion. Patients with two or more preoperative risk factors should be cautiously selected for liver resection. | 18,835,514 |
Characterization of ornithine and glutamine lipids extracted from cell membranes of Rhodobacter sphaeroides. | The identification and structural characterization of a series of ornithine lipids extracted from the cell membranes of wild-type Rhodobacter sphaeroides, as well as from a glycerophosphocholine-deficient strain, have been achieved by multistage tandem mass spectrometry of their protonated and deprotonated precursor ions in a linear quadrupole ion trap. Systematic examination of the multistage gas-phase fragmentation reactions of these ions, combined with the use of hydrogen/deuterium exchange, has enabled the pathways responsible for sequential losses of the 3-hydroxy linked fatty acyl chain and the amide linked 3-OH fatty acyl chain from these lipids, as well as for formation of the previously reported ornithine specific positively charged "fingerprint" ion at m/z 115, to be determined. Additionally, the fragmentation pathways responsible for formation of a previously unreported ornithine lipid head group-specific product ion at m/z 131 in negative ion mode have been examined. Based on these results, and by comparison with the fragmentation behavior of model lipoamino acid standard compounds, a series of novel glutamine containing lipids have also been identified, with analogous structures but with masses 14 Da higher than those of several of the ornithine lipids observed in this study. Characteristic "fingerprint" ions indicative of these glutamine lipids were found at m/z 147, 130, and 129 in positive ion mode and at m/z 145 and 127 in negative ion mode. The results from this study establish an experimental basis for future efforts aimed at the sensitive identification, characterization, and quantitative analysis of ornithine and glutamine lipids in complex unfractionated cellular extracts. | 18,835,523 |
Three dimensional morphometric analyses of axon terminals early changes induced by methylmercury intoxication in the adult cat striate cortex. | The aim of the present report is to investigate in detail morphometric changes of axon terminals of area 17 of adult cat induced by methylmercury intoxication. Six adult male cats (Felix catus), with 12 h day-light cycle and ad libitum water and food regimen, received a single dose of MeHgCl (6.4 mg/kg) dissolved in milk, whereas control subjects (n=6) received only milk. After 30 days, biocytin iontophoretic injections were done into the area 17, (Horsley-Clark coordinates between AP 3.0-6.0) on the crown of the lateral gyrus, near the border with area 18. MeHg and inorganic Hg (Hgi) concentrations were measured in the brain parenchyma of intoxicated cats and corresponded on average to 1.39+/-0.3 and 6.79+/-0.6 ppm (mean+/-s.e.m.) respectively. Twenty four hours after iontophoresis, aldehyde fixed brain sections (200 microm thick), were processed to reveal biocytin labeled terminals. Axonal microscopic 3D reconstructions using Neurolucida software (Microbright Systems Inc.) allowed estimations of boutons, branching points and segment densities for each terminal. Cluster analysis of morphometric axonal features from control and intoxicated group revealed, two distinct axon families (Type I and II) as described elsewhere. Total density values of boutons, branching points and segment densities of intoxicated group, decreased 81, 59 and 91% respectively, as compared to the control group (ANOVA two-way, Bonferroni a priori test p<0.05). Altered axonal morphology associated with MeHg, appeared early in the disease (30 days after contamination), revealing new aspects of the neuronal pathology of the methylmercury intoxication in the visual cortex. | 18,835,550 |
Regulation of root elongation by histone acetylation in Arabidopsis. | Transcriptional repression by histone modification represents a universal mechanism that underlies critical biological processes, such as neurogenesis and hematopoietic differentiation, in animals. In plants, however, the extent to which these regulatory pathways are involved in development and morphogenesis is not well defined. SWP1/LDL1 is a component of a plant corepressor complex that is involved in regulation of flower timing. Here, we report that SWP1 also plays a role in the regulation of root elongation by repressing a root-specific gene lateral root primordium 1 (LRP1) via histone deacetylation. A null mutation in SWP1 results in hyperacetylation of histones H3 and H4 in LRP1 chromatin, elevation of LRP1 expression, and increased root elongation. This effect of SWP1 knockout on the root phenotype is mimicked by transgenic expression of LRP1, which bypasses the SWP1-mediated suppression of the native gene. Thus, SWP1 likely functions as a regulator of developmental events both in the shoot and in the root meristem. | 18,835,563 |
Engagement of TLR signaling as adjuvant: towards smarter vaccine and beyond. | Toll like receptors (TLRs) are a family of conserved pattern recognition receptors that recognizes specific microbial patterns and allow the cell to distinguish between self and non-self materials. The very property of the TLRs to link innate and adaptive immunity offers a novel prospect to develop vaccines engaging TLR signaling. The presence of TLR ligands as adjuvant in conjunction with the vaccine is shown to increase the efficacy and response to the immunization with a particular antigen. For infectious as well as for noninfectious diseases, TLR activation have been used in both established and experimental vaccines. The choice of the TLR agonist to be used, the subsequent efficacy and the safety profile of the vaccine is thus a crucial step in vaccine development. Recent studies also suggest the involvement of other non-TLR immune receptors to control vaccine immunogenicity. Here we focus on the findings dealing with TLR ligands as adjuvant and discuss the importance of these studies to develop an optimal vaccine. | 18,835,576 |
Characterization of the hemoglobins of the Australian lungfish Neoceratodus forsteri (Krefft). | We examined for the first time the hemoglobin components of the blood of the Australian lungfish, Neoceratodus forsteri and their functional responses to pH and the allosteric modulators adenosine triphosphate (ATP), guanosine triphosphate (GTP), 2,3-bisphosphoglyceric acid (BPG) and inositol hexaphosphate (IHP) at 25 degrees C. Lysates prepared from stripped, unfractionated hemolysate produced sigmoidal oxygen equilibrium curves with high oxygen affinity (oxygen partial pressure required for 50% hemoglobin saturation, p(50)=5.3 mmHg) and a Hill coefficient of 1.9 at pH 7.5. p(50) was 8.3 and 4.5 mmHg at pH 6 and 8, respectively, which corresponded to a modest Bohr coefficient (Delta log p(50)/Delta pH) of -0.13. GTP increased the pH sensitivity of oxygen binding more than ATP, such that the Bohr coefficient was -0.77 in the presence of 2 mmol L(-1) GTP. GTP was the most potent regulator of hemoglobin affinity, with concentrations of 5 mmol L(-1) causing an increase in p(50) from 5 to 19 mm Hg at pH 7.5, while the order of potency of the other phosphates was IHP>ATP>BPG. Three hemoglobin isoforms were present and each contained both alpha and beta chains with distinct molecular weights. Oxygen affinity and pH-dependence of isoforms I and II were essentially identical, while isoform III had a lower affinity and increased pH-dependence. The functional properties of the hemoglobin system of Neoceratodus appeared consistent with an active aquatic breather adapted for periodic hypoxic episodes. | 18,835,585 |
Normothermic and hypothermic models for studying the deleterious effects of hypoxia-reoxygenation on EDHF-mediated relaxation in isolated porcine coronary arteries. | The vasomotor response of the coronary artery is altered by hypoxia-reoxygenation (H-R) induced damage. The aim of our study was to compare and evaluate normothermic and hypothermic models which are suitable for future drug studies of vasoprotective action against H-R injury. Porcine coronary arterial rings were isolated and placed in Krebs-Henseleit (K-H) solution. Rings were exposed to normoxic conditions (control group) and two different H-R conditions: the first induced by a 95% N(2)-5% CO(2) gas mixture (40- and 60-min hypoxia) in a normothermic protocol, and the second induced by hypothermic (4 degrees C) hypoxia-reoxygenation in an air-tight beaker filled with K-H solution (24- and 48-hours hypoxia). Reoxygenation was applied by introducing K-H solution aerated with a 95% O(2)-5% CO(2) mixture under normothermic (37 degrees C) conditions. To test the EDHF-mediated relaxation by substance P, rings were first incubated in L-NNA, nitric oxide synthase inhibitor, and indomethacin, cyclooxygenase inhibitor, and then pre-contracted with thromboxane analogue U-46619. Analysis of the maximum relaxation of the arterial rings was performed by one-way ANOVA, followed by Bonferroni's post-test. Distal segments of the coronary artery responded faster to contraction induced by U-46619 and were relaxed by substance P to a greater extent than proximal segments. Maximal relaxations of arterial rings induced by a 10 nM solution of substance P were significantly reduced (p<0.001) from the values for normoxic rings (81.0+/-1.0%, n=30) after 40-min H-R (50.5+/-5.3%, n=30), 60-min H-R (32.1+/-3.5%, n=30), 24-hours hypothermic H-R (56.0+/-2.3%, n=30) and after 48-hours hypothermic H-R (38.5+/-5.1%, n=30). The model employing 40-min normothermic H-R is as effective as 24-hours hypothermic H-R, and 60-min normothermic H-R as 48-hours hypothermic H-R for studying the deleterious effects of H-R on EDHF-mediated relaxation. | 18,835,583 |
[De Seze et al. criteria: application to a series of 14 patients presenting a first severe acute demyelinating event]. | The application of de Seze et al. criteria (2007) to patients presenting a first severe acute demyelinating event helps to distinguish acute disseminated encephalomyelitis (ADEM) from other CNS inflammatory diseases, with 83% sensitivity and 95% specificity. We applied these criteria to 14 patients who presented a first severe acute demyelinating event and whose later clinical course enabled clear identification of the neurological diagnosis. This study concerned 14 patients who presented a first acute demyelinating event. Initially, there were 16 patients but two were excluded because their initial clinical condition (isolated acute retrobulbar optic neuritis in one and acute cervical myelitis in the other) would have excluded them in the princeps article. We identified 11 women (78.6%) and three men (21.4%) with a mean age of 33.7+/-12.5 years. Follow-up ranged from three months to 11.5 years after the initial episode (average four years). At last follow-up, the diagnosis was ADEM in seven patients (50%) and multiple sclerosis (MS) in seven (50%). Five of seven patients in the MS group had a tumor-like presentation (71.4%), this parameter partly explaining the initial discrepancy in diagnosis. When applied to our series, de Seze criteria for ADEM exhibited 85.7% sensitivity and 71.4% specificity. Applying the new criteria, we did not find the same sensitivity, specificity, and positive and negative predictive values as in the original article. The lack of specificity arose from the misclassification of MS patients with a tumor-like presentation (two out of five false negatives). One of the explanations is that the clinical criteria used can be part of atypical forms of MS, in particular in its tumor-like presentation. De Seze et al. criteria can be an invaluable help for the clinician in the diagnosis of a first severe demyelinating event. Considering our results, these criteria should not be applied for patients with a tumor-like form of MS. A prospective study in a larger cohort is needed to confirm or invalidate these preliminary results. | 18,835,615 |
Mass balance and isotope effects during nitrogen transport through septic tank systems with packed-bed (sand) filters. | Septic tank systems are an important source of NO3(-) to many aquifers, yet characterization of N mass balance and isotope systematics following septic tank effluent discharge into unsaturated sediments has received limited attention. In this study, samples of septic tank effluent before and after transport through single-pass packed-bed filters (sand filters) were evaluated to elucidate mass balance and isotope effects associated with septic tank effluent discharge to unsaturated sediments. Chemical and isotopic data from five newly installed pairs and ten established pairs of septic tanks and packed-bed filters serving single homes in Oregon indicate that aqueous solute concentrations are affected by variations in recharge (precipitation, evapotranspiration), NH4+ sorption (primarily in immature systems), nitrification, and gaseous N loss via NH3 volatilization and(or) N2 or N2O release during nitrification/denitrification. Substantial NH4+ sorption capacity was also observed in laboratory columns with synthetic effluent. Septic tank effluent delta15N-NH4+ values were almost constant and averaged +4.9 per thousand+/-0.4 per thousand (1 sigma). In contrast, delta15N values of NO3(-) leaving mature packed-bed filters were variable (+0.8 to +14.4 per thousand) and averaged +7.2 per thousand+/-2.6 per thousand. Net N loss in the two networks of packed-bed filters was indicated by average 10-30% decreases in Cl(-)-normalized N concentrations and 2-3 per thousand increases in delta15N, consistent with fractionation accompanying gaseous N losses and corroborating established links between septic tank effluent and NO3(-) in a local, shallow aquifer. Values of delta18O-NO3(-) leaving mature packed-bed filters ranged from -10.2 to -2.3 per thousand (mean -6.4 per thousand+/-1.8 per thousand), and were intermediate between a 2/3 H2O-O+1/3 O2-O conceptualization and a 100% H2O-O conceptualization of delta18O-NO3(-) generation during nitrification. | 18,835,629 |
The masticator space: from anatomy to pathology. | The masticator space is a deep facial space with a complex anatomical structure. The purpose of the present study was to precisely define the masticator space to eliminate the use of obsolete and confusing terms to describe the area, and to illustrate the common mass syndromes. Primary tumors are uncommon, usually benign and of a vascular or neural origin. Adjacent lesions, mainly pharyngeal with secondary extension into the masticator space, are especially frequent. Metastases are rare, and infectious pathology is often odontogenic. The most frequent lesion of the masticator space is the odontogenic abscess. Multidetector CT and MRI enable precise study of the space, its communications with other deep spaces and the etiology of any mass syndrome. Understanding the anatomy of the masticator space and how it links up with the other deep facial spaces helps the radiologist to recognize the different lesions of this space and to avoid unnecessary surgery, or any other less than optimal management. | 18,835,644 |
[Uncommon manifestation revealing sarcoidosis]. | Bilateral hilar lymphadenopathy, with or without lung parenchymal infiltrates, is the most common radiographic finding in patients with sarcoidosis. Atypical pulmonary findings have been uncommonly reported and include multiple large lung nodules, cavitation, lobar collapse, pleural effusions or pneumothorax. We report a 21-year-old non caucasian patient who presented with pulmonary nodular infiltration and sinonasal involvement revealing sarcoidosis. Thoracic and sinus computed tomographic scan showed both multiple excavated large lung nodules and micronodules, hilar lymphadenopathy and sinus thickening. Laboratory studies disclosed elevated angiotensin converting enzyme serum level (120UI/L). Outcome was favorable after institution of corticosteroids (at an initial dose of prednisone of 1mg/kg/day); at eight-month-follow-up, the patient was asymptomatic, while receiving prednisone 22.5mg/day. In patients exhibiting unusual pulmonary manifestations, diagnosis of sarcoidosis relies on compatible clinical signs, evidence of non-caseating granulomas, and exclusion of underlying conditions including infections, malignancy and other granulomatous diseases (Wegener disease, pneumoconiosis). | 18,835,653 |
A novel approach to reduce hemorrhagic transformation after interventional management of acute stroke: catheter-based selective hypothermia. | Interventional management of acute stroke can significantly increase recanalization rate of the occluded artery, however, this improvement is achieved at the expense of an increased incidence in symptomatic intracranial hemorrhage, which may markedly reduce the therapeutic benefit of this treatment. Hypothermia is one of the most promising neuroprotective approaches studied. It may also lower the risk of postischemic hemorrhage by reducing the activities of matrix metalloproteinases and blood-brain barrier disruption. But in most clinical studies, hypothermia is induced by surface cooling. It has two major drawbacks. (1) Several hours are required to reach the target body core temperature. (2) The incidence of adverse effects, such as impaired immune function, shivering, pneumonia, and cardiac arrhythmias/bradycardias, is high. Selective brain hypothermia without reducing body core temperature can theoretically address both problems of whole body cooling. So it is hypothesized that interventional management of acute stroke combined with catheter-based selective brain hypothermia may reduce the risk of postischemic hemorrhagic transformation, at the same time circumventing the bulk of negative side effects associated with systemic hypothermia. | 18,835,666 |
Synchronisation of ovarian follicular waves in the dromedary camel (Camelus dromedarius). | This study was designed to compare the efficacy of various treatments intended to synchronise follicular wave cycles in dromedary camels by removing the existing follicle of unknown size and replacing it with a follicle capable of ovulating at a known time. Camels were randomly assigned to one of five groups and treated with either (1) 5mg oestradiol benzoate (i.m.) and 100mg progesterone (i.m.; E/P, n=15), (2) 20 icrog GnRH analogue, buserelin (i.m.; GnRH, n=15), (3) 20 microg buserelin (i.m.) on Day 0 (T=0) and 500 microg prostaglandin on Day T+7 (GnRH/PG n=15), (4) transvaginal ultrasound-guided follicle ablation of all follicles > or =0.5 cm (ABL, n=15) or (5) 5 ml saline (i.m; Controls n=15). All camels were subsequently injected with 20 microg buserelin 14 days after the first treatment was given. The ovarian response was monitored daily by transrectal ultrasonography and the intervals from treatment to follicular wave emergence and also the day on which the new dominant follicle reached 1.3 cm was recorded. Amongst the treatment groups the mean interval from treatment to new follicle wave emergence and treatment to time taken for the new dominant follicle to reach 1.3 cm in diameter was shortest in the ABL group (2.3+/-0.5 days and 8.8+/-1.1 days respectively, P=0.044) and longest in the E/P group (6.4+/-0.8 days and 12.2+/-1.0 days respectively, P<0.001) whereas the GnRH and GnRH/PG groups were intermediate (3.0+/-0.5 days and 11.1+/-0.8 days GnRH; and 4.5+/-0.5 days and 10.7+/-0.7 days GnRH/PG). A total of 11/15 camels in both the GnRH and GnRH/PG groups had dominant follicles between 1.3 and 1.9 cm 14 days post treatment, of which 21 of the 22 follicles ovulated after GnRH injection on T+14. The ABL, E/P and control groups however, showed greater variability in follicle size with less camels having dominant follicles between 1.3 and 1.9 cm than the GnRH and GnRH/PG groups and more in the > or =2.0 cm or follicle regressing groups, therefore fewer of these camels ovulated (ABL n=7; E/P n=9; Control n=6) after GnRH injection on Day T+14. In conclusion, two GnRH injections 14 days apart or two GnRH injections 14 days apart and PG on Day 7 after the first GnRH were the most effective methods to synchronise ovulation rate in dromedary camels at a fixed time interval of 14 days after treatment. | 18,835,669 |
Cyclodextrin-based potentiometric sensors for midazolam and diazepam. | In this work the implementation of benzodiazepine ion-selective electrodes for pharmaceutical formulations control is described. The solid-contact electrodes for midazolam and diazepam are based on polymeric membranes incorporating respectively beta-cyclodextrin and (2-hydroxiproyl)-gamma-cyclodextrin as ionophores, 2-fluorophenyl 2-nitrophenyl ether as plasticizer and potassium tetrakis (p-chlorophenyl) borate as ionic additive. For conventionally shaped midazolam electrode a slope of 61.9+/-1.3 mVdec(-1), a LLLR of 5.7+/-2.7 x 10(-4)gL(-1) and pH range of 2.6-5.4 was obtained, while the corresponding values for diazepam electrodes were of 67.6+/-3.0 mVdec(-1), 4.9+/-1.5 x 10(-2)gL(-1) and 1.9-2.7 pH units, respectively. Membrane optimization was based on the molar ratio between the ionophore and additive for midazolam and on inclusion cavity of cyclodextrin for diazepam. The miniaturization of the above-described electrodes gave rise to potentiometric detectors for sequential-injection lab-on-valve system with similar characteristics albeit the useful lifetime shortened from 1 year to approximately 15 days under continuous operation. The optimized flow conditions were achieved for sample injection volumes of 20 microL propelled towards the detection cell at the flow rate of 16 microLs(-1) during 80s. Real sample analysis revealed statistical accuracy and between-days precision comparable to the general used chromatographic-based procedure. | 18,835,673 |
Measuring the quality of substance use disorder treatment: evaluating the validity of the Department of Veterans Affairs continuity of care performance measure. | This study examined the patient- and facility-level associations between the continuity of care performance measure adopted by the Department of Veterans Affairs (VA) and improvements in self-administered Addiction Severity Index (ASI) composites and other indicators of problematic substance use. Up to 50 patients from each of a nationally representative sample of 109 VA substance use disorder (SUD) treatment programs at 73 VA facilities were assessed at intake and posttreatment. The continuity of care performance measure specifies that patients should receive at least two SUD outpatient visits in each of the three consecutive 30-day periods after they qualify as new SUD patients. In analyses adjusting for baseline characteristics, meeting the continuity of care performance measure was not associated with patient-level improvements in the ASI alcohol or drug composites, days of alcohol intoxication, or days of substance-related problems. Facility-level rates of continuity of care were negatively associated with improvements in ASI alcohol and drug composites. The continuity of care performance measure derived from prior patient-level evidence did not discriminate facility-level performance as predicted. Translating research into process-of-care quality measures requires postconstruction validation. | 18,835,678 |
Predictors of opiate agonist treatment retention among injection drug users referred from a needle exchange program. | The aim of this study was to examine the effect of a case management intervention on retention in opiate agonist therapy among injection drug users (IDUs) referred from a needle exchange program (NEP). DESIGN, INTERVENTION, PARTICIPANTS, AND SETTING: A randomized trial of a strengths-based case management intervention versus passive referral (control) was conducted among NEP attendees requesting and receiving referrals to subsidized, publicly funded opiate agonist treatment programs in Baltimore, MD. Multivariable Cox regression models were used to identify predictors of treatment retention using an ecological model approach, taking into account factors at the individual, social, and environmental level. Of 245 IDUs, 127 (51.8%) entered opiate agonist treatment, for whom median retention was 7.9 months. The intervention was not associated with longer retention (p = .91). Individual-level factors predictive of shorter retention included being employed and greater levels of psychiatric distress. Participants who had prior treatment experience and multiple treatment requests were retained significantly longer. Social factors adversely affecting treatment retention included unstable housing and buying drugs for others. Living further away from the treatment site was an environmental barrier that negatively affected treatment retention. Multilevel interventions that address individual, social, and environmental factors are necessary to improve substance abuse treatment retention and treatment outcomes among IDUs referred from NEP. | 18,835,681 |
Residence time dependent desorption of Staphylococcus epidermidis from hydrophobic and hydrophilic substrata. | Adhesion and desorption are simultaneous events during bacterial adhesion to surfaces, although desorption is far less studied than adhesion. Here, desorption of Staphylococcus epidermidis from substratum surfaces is demonstrated to be residence time dependent. Initial desorption rate coefficients were similar for hydrophilic and hydrophobic dimethyldichlorosilane (DDS)-coated glass, likely because initial desorption is controlled by attractive Lifshitz-Van der Waals interactions, which are comparable on both substratum surfaces. However, significantly slower decay times of the desorption rate coefficients are found for hydrophilic glass than for hydrophobic DDS-coated glass. This difference is suggested to be due to the acid-base interactions between staphylococci and these surfaces, which are repulsive on hydrophilic glass and attractive on hydrophobic DDS-coated glass. Final desorption rate coefficients are higher on hydrophilic glass than on hydrophobic DDS-coated glass, due to the so called hydrophobic effect, facilitating a closer contact on hydrophobic DDS-coated glass. | 18,835,700 |
Health and healthcare perspectives of African American residents of an unincorporated community: a qualitative assessment. | Residential perspectives about health in unincorporated communities are virtually unexplored. In this study, we conducted focus groups to assess individual and community health status, environmental health mediators, and systematic barriers to healthcare among African American residents of the unincorporated town, Fresno, Texas. Residents described their individual health status as excellent, but depicted the community's health status as fair. Unaffordable healthcare, limited access to healthcare, and environmental mediators were perceived to impact the Fresno community's health status. Our findings suggest a need to begin to examine health outcomes for minority residents in other unincorporated communities. | 18,835,739 |
High resolution topographical mapping of warm and cold sensitivities. | This study aims to explore the thermal sensitivity distribution (topographical mapping) over the glabrous skin of the hand in males and females. Warm (WT) and cold (CT) thresholds were measured in 25 healthy volunteers (12 females), applying a multi-site test of 23 locations on the volar part of the hand. The palm area was more sensitive than the fingers to both warm (P<0.001) and cold (P<0.001) stimuli. On the palm itself, the proximal part was the most sensitive (P<0.05). Heterogeneity was also found to both warm and cold sensibilities within dermatomes (P<0.05) as well as to cold sensitivity across dermatomes (P<0.001). Females were more sensitive than males to both warm (P<0.001) and cold sensations (P<0.001). In addition, painful components were frequently reported as accompanying warm/cold sensations during mild warming/cooling. The thermal sensitivity distribution over the glabrous skin of the hand is highly heterogeneous. It is appropriate to precisely define testing locations when conducting thermal examinations on the hand. | 18,835,741 |
Immunological commonalities and distinctions between airway and digestive immunity. | Airway and digestive tissues are the frontlines of the body's defense, being continuously exposed to the outside environment and encountering large numbers of antigens and microorganisms. To achieve immunosurveillance and immunological homeostasis in the harsh environments of the mucosal surfaces, the mucosal immune system tightly regulates a state of opposing but harmonized immune activation and quiescence. Recently, accumulating evidence has revealed that although the respiratory and intestinal immune systems share common mucosa-associated immunological features that are different from those of the systemic immune system, they also show distinctive immunological phenotypes, functions, and developmental pathways. We describe here the common and distinct immunological features of respiratory and intestinal immune systems and its application to the development of mucosal vaccines. | 18,835,748 |
Influence of subtraction ictal SPECT on surgical management in focal epilepsy of indeterminate localization: a prospective study. | The impact of functional imaging tests on the decision-making and planning process for epilepsy surgery has never been prospectively assessed. We prospectively evaluated 50 consecutively eligible patients whose noninvasive evaluations showed nonlocalized findings and determined how their SISCOM (subtraction ictal SPECT [single photon emission computed tomography] co-registered to MRI [magnetic resonance imaging]) data altered consensus decisions for epilepsy surgery. At an epilepsy surgery conference where each patient was discussed, consensus decisions were documented after a standardized presentation of data from the noninvasive evaluation (SISCOM findings initially were excluded). Consensus decisions were again documented after presentation of SISCOM data. Consensus decisions changed for 10 of 32 patients (31%) with localizing SISCOM results, whereas the decision changed in only 1 of 18 patients (6%) with nonlocalizing SISCOM results (P<.05). Changes in consensus decisions were as follows: (1) intracranial electrode implantation (IEI) was obviated and resective surgery was recommended (n=2); (2) resective surgery or further evaluation for patients initially not considered surgical candidates (n=2); (3) IEI in patients for whom it was not recommended initially (n=3); (4) increased IEI coverage (n=3); and (5) antiepileptic drug trial or vagal nerve stimulation was recommended instead of IEI (n=1). For some patients whose noninvasive evaluations did not clearly localize a surgical focus, SISCOM data can have a major impact on decisions to recommend resective epilepsy surgery or IEI. | 18,835,758 |
Histopathological lesions following intramuscular administration of saline in laboratory rodents and rabbits. | This review was undertaken to assess the nature and incidence of procedure-related changes in mice, rats and rabbits which received saline solution by intramuscular injection. Data were collected on the injection sites from 7 studies representing 152 animals. The original observations by the different study pathologists from both control and treated animals were evaluated in order to create a glossary of preferred terms to be used in toxicology studies. These standardized terms were then applied to changes observed in the saline-treated animals. The review showed that the most severe of the procedure-related lesions were only of a slight level. Two days post-injection, the local reactions were mainly composed of minimal infiltration by mononuclear cells (lymphocytes and macrophages) with occasional degeneration of myofibres. From 10 to 42 days post-injection, lesions showed regeneration of myofibres and some fibrosis. In rats, the number of injections at each site influenced inflammatory infiltrate and degenerative lesions. | 18,835,765 |
Magnetic resonance imaging of heterotaxis syndrome. | Failure to establish normal left-right body axis (LRA) formation during embryogenesis results in heterotaxis, a multi-malformation syndrome. We report on a 20-year-old young woman who presented to the emergency room with upper abdominal pain. On chest X-ray, dextrocardia was noted. Ultrasound was inconclusive. Barium studies demonstrated non-rotation of the intestine. Magnetic resonance imaging (MRI) of the abdomen confirmed heterotaxis with abnormal arrangement of abdominal organs and vasculature. This is the first radiographic description of LRA in MRI. It provides a unique contribution to the wide morphological variety of lateralization defects in a single examination within 15 min and without the risks of ionizing radiation. In addition, a literature overview over the genetic aspects, broad morphological spectrum, and possible therapeutic consequences is given. | 18,835,766 |
Tissue processing of nitrite in hypoxia: an intricate interplay of nitric oxide-generating and -scavenging systems. | Although nitrite (NO(2)(-)) and nitrate (NO(3)(-)) have been considered traditionally inert byproducts of nitric oxide (NO) metabolism, recent studies indicate that NO(2)(-) represents an important source of NO for processes ranging from angiogenesis through hypoxic vasodilation to ischemic organ protection. Despite intense investigation, the mechanisms through which NO(2)(-) exerts its physiological/pharmacological effects remain incompletely understood. We sought to systematically investigate the fate of NO(2)(-) in hypoxia from cellular uptake in vitro to tissue utilization in vivo using the Wistar rat as a mammalian model. We find that most tissues (except erythrocytes) produce free NO at rates that are maximal under hypoxia and that correlate robustly with each tissue's capacity for mitochondrial oxygen consumption. By comparing the kinetics of NO release before and after ferricyanide addition in tissue homogenates to mathematical models of NO(2)(-) reduction/NO scavenging, we show that the amount of nitrosylated products formed greatly exceeds what can be accounted for by NO trapping. This difference suggests that such products are formed directly from NO(2)(-), without passing through the intermediacy of free NO. Inhibitor and subcellular fractionation studies indicate that NO(2)(-) reductase activity involves multiple redundant enzymatic systems (i.e. heme, iron-sulfur cluster, and molybdenum-based reductases) distributed throughout different cellular compartments and acting in concert to elicit NO signaling. These observations hint at conserved roles for the NO(2)(-)-NO pool in cellular processes such as oxygen-sensing and oxygen-dependent modulation of intermediary metabolism. | 18,835,812 |
Single-step purification of pepsin-derived monoclonal antibody fragments from crude murine ascitic fluids by ceramic hydroxyapatite high-performance liquid chromatography. | Ceramic hydroxyapatite (CHT) high-performance liquid chromatography (HPLC) is used to purify a variety of classes of monoclonal antibodies (mAbs) from crude murine ascites fluids. We report here that this method is also applicable for simple and efficient purification of many mAb fragments that are generated by pepsin treatment of crude ascites. F(ab')(2) fragments were quantitatively generated from IgG(1) mAbs in ascitic fluids by incubation with pepsin for 6 h at pH 3.9-4.1. Under the same conditions, pepsin also cleaved unwanted ascites components, such as albumin and transferrin to very low molecular weight polypeptides. The F(ab')(2) fragments, but not the low molecular weight products, selectively bound to and were eluted from the CHT column using a linear gradient of phosphate ion concentration over 15 min. The recovery of the F(ab')(2) fragments by CHT-HPLC was >90%. This method also allowed single-step purification of mAb fragments from distinct IgG subclasses (IgG(2a) and IgG(2b)) and IgM directly from crude digested ascitic samples. This CHT-HPLC method combined with direct pepsinolysis of murine ascites is a useful strategy for rapid purification and characterization of many types of mAb fragments. | 18,835,826 |
Comparing expression of progesterone and estrogen receptors in testicular tissue from men with obstructive and nonobstructive azoospermia. | The objective of this study was to identify and compare the expression profiles of progesterone receptor (PR) and estrogen receptor alpha (ERalpha) in the testes of men with obstructive azoospermia (OA), maturation arrest (MA), and Sertoli cell-only (SCO) histology. Testicular biopsies were obtained from 10 patients with OA, 10 patients with MA (either early or late arrest), and 8 patients with SCO who did not have hormonal abnormalities and varicoceles. Expression of PR and ERalpha was detected by immunofluorescence and Western blot. PR was expressed in the spermatogenic, Leydig, and Sertoli cells in the testes of OA patients. In the MA and SCO patients, the expression of PR was reduced in all cell types as compared with that in the OA patients. Western blot demonstrated that both the full-size (120 KDa) and the truncated (52 KDa) isoforms of the PR were expressed in the OA and MA testes. However, in the SCO testes, only the truncated isoform of PR (52 KDa) was expressed. ERalpha (66 KDa) was expressed principally in the spermatogenic and Leydig cells in the OA testes. By immunohistochemistry staining, expression of ERalpha was decreased in the spermatogenic and Leydig cells of the MA testes, whereas its expression was enhanced in the Leydig cells of the SCO testes. However, by Western blot, expression of ERalpha was significantly reduced in the SCO testes as compared with that in the OA and MA testes. We conclude that PR and ERalpha may play a role in the pathogenesis of the MA and SCO phenotype in patients with infertility. | 18,835,831 |
Association of adiposity status and changes in early to mid-adulthood with incidence of Alzheimer's disease. | Adiposity status and change are potential risk factors for Alzheimer's disease (AD). The authors used data on 2,322 participants in the Baltimore Longitudinal Study of Aging to analyze the relation between AD incidence and adiposity in Cox proportional hazards models, with adjustment for sociodemographic factors and smoking status. Body mass index (BMI; weight (kg)/height (m)(2)) and waist circumference at specific ages were predicted by empirical Bayes estimators from mixed-effects regression models. After a median of 23.4 years of follow-up between 1958 and 2006, 187 participants developed AD. Among men, being underweight (BMI <or=18.5) at age 30, 40, or 45 years increased the likelihood of AD (hazard ratio (HR) = 5.76, 95% confidence interval (CI): 2.07, 16.00); among women, being obese (BMI >or=30) at age 30, 40, or 45 years and jointly centrally obese (waist circumference >or=80th percentile) at age 30, 35, or 50 years increased AD risk (HR = 6.57, 95% CI: 1.96, 22.02). Women who lost weight (BMI change <10th percentile) between ages 30 and 45 years were also at increased risk (HR = 2.02, 95% CI: 1.06, 3.85). Weight gain among men (BMI change >90th percentile) between ages 30 and 50 years increased AD risk (HR = 3.70, 95% CI: 1.43, 9.56). Future studies should identify age- and gender-specific optimal weights and weight-loss strategies for preventing AD and investigate potential mechanisms. | 18,835,864 |
Accuracy of dementia diagnosis: a direct comparison between radiologists and a computerized method. | There has been recent interest in the application of machine learning techniques to neuroimaging-based diagnosis. These methods promise fully automated, standard PC-based clinical decisions, unbiased by variable radiological expertise. We recently used support vector machines (SVMs) to separate sporadic Alzheimer's disease from normal ageing and from fronto-temporal lobar degeneration (FTLD). In this study, we compare the results to those obtained by radiologists. A binary diagnostic classification was made by six radiologists with different levels of experience on the same scans and information that had been previously analysed with SVM. SVMs correctly classified 95% (sensitivity/specificity: 95/95) of sporadic Alzheimer's disease and controls into their respective groups. Radiologists correctly classified 65-95% (median 89%; sensitivity/specificity: 88/90) of scans. SVM correctly classified another set of sporadic Alzheimer's disease in 93% (sensitivity/specificity: 100/86) of cases, whereas radiologists ranged between 80% and 90% (median 83%; sensitivity/specificity: 80/85). SVMs were better at separating patients with sporadic Alzheimer's disease from those with FTLD (SVM 89%; sensitivity/specificity: 83/95; compared to radiological range from 63% to 83%; median 71%; sensitivity/specificity: 64/76). Radiologists were always accurate when they reported a high degree of diagnostic confidence. The results show that well-trained neuroradiologists classify typical Alzheimer's disease-associated scans comparable to SVMs. However, SVMs require no expert knowledge and trained SVMs can readily be exchanged between centres for use in diagnostic classification. These results are encouraging and indicate a role for computerized diagnostic methods in clinical practice. | 18,835,868 |
The effect of a 'vanishing twin' on biochemical and ultrasound first trimester screening markers for Down's syndrome in pregnancies conceived by assisted reproductive technology. | Previous studies have found that 1 in 10 in vitro fertilization (IVF) singletons originates from a twin gestation. First trimester Down's syndrome screening markers are altered in assisted reproductive techniques (ART) pregnancies compared with spontaneously conceived pregnancies. The presence of a perished embryo may further complicate prenatal screening among women pregnant after ART. The aim of this study was to assess the impact of a 'vanishing twin' on first trimester combined biochemical and ultrasound screening in pregnancies conceived after IVF and intracytoplasmatic sperm injection. From a national prospective cohort study concerning first trimester combined screening among women pregnant after ART, 56 cases of pregnancies with a vanishing twin were identified. As control group 897 cases of ART singleton pregnancies were used. All women completed a first trimester combined ultrasound and biochemical screening programme comprising serum PAPP-A and free beta-hCG together with nuchal translucency (NT) measurement. There were no significant differences in geometric mean MoM free beta-hCG and PAPP-A between pregnancies with an early (gestational week <9, EVT) or late vanishing twin (gestational week 9-13, LVT) or singleton pregnancies (0.98, 1.13 and 0.95 for free beta-hCG and 0.84, 0.80 and 0.74 for PAPP-A, respectively). Likewise, no difference was seen for NT measurements. The gestational age at the time of blood sampling and NT scan was similar for the three groups. The proportion of EVT pregnancies with a PAPP-A and free beta-hCG log(10)MoM value below the 5th%iles and above the 95th%iles of the value in the singleton pregnancies were 4.3%, 4.3%, 6.4% and 8.5%, respectively, which did not constitute a significant difference from singletons. The corresponding values for LVT pregnancies were 0%, 22.2%, 0% and 11.1%, respectively; however, these numbers were too small to allow for statistical calculations. First trimester biochemical screening markers in women pregnant after ART, and with a vanished twin diagnosed at early ultrasound, do not differ from those of other ART singleton pregnancies. In cases where the fetal demise was first diagnosed at the time of the NT scan, it is doubtful whether the serum risk assessment is as precise as it is in singleton ART pregnancies. No difference was seen for NT measurements. | 18,835,870 |
Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis. | The heritability of RA has been estimated to be approximately 55%, of which the MHC contributes about one-third. HLA-DRB1 alleles are strongly associated with RA, but it is likely that significant non-DRB1 MHC genetic susceptibility factors are involved. Previously, we identified two three-marker haplotypes in a 106-kb region in the MHC class III region immediately centromeric to TNF, which are strongly associated with RA on HLA-DRB1*0404 haplotypes. In the present study, we aimed to refine these associations further using a combination of genotyping and gene expression studies. Thirty-nine nucleotide polymorphisms (SNPs) were genotyped in 95 DRB1*0404 carrying unrelated RA cases, 125 DRB1*0404-carrying healthy controls and 87 parent-case trio RA families in which the affected child carried HLA-DRB1*04. Quantitative RT-PCR was used to assess the expression of the positional candidate MHC class III genes APOM, BAT2, BAT3, BAT4, BAT5, AIF1, C6orf47, CSNK2beta and LY6G5C, and the housekeeper genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and beta(2)-microglobulin (B2M) in 31 RA cases and 21 ethnically, age- and sex-matched healthy controls. Synovial membrane specimens from RA, PsA and OA cases were stained by an indirect immunoperoxidase technique using a mouse-anti-human AIF1 monoclonal antibody. Association was observed between RA and single markers or two marker haplotypes involving AIF1, BAT3 and CSNK. AIF1 was also significantly overexpressed in RA mononuclear cells (1.5- to 1.9-fold difference, P = 0.02 vs HPRT, P = 0.002 vs B2M). AIF1 protein was clearly expressed by synovial macrophages in all the inflammatory synovial samples in contrast to the non-inflammatory OA samples. The results of the genotyping and expression studies presented here suggest a role for AIF1 in both the aetiology and pathogenesis of RA. | 18,835,879 |
The effect of glycosylation on interparticle interactions and dimensions of native and denatured phytase. | Glycosylation affects the physical properties of proteins in a number of ways including solubility and aggregation behavior. To elucidate the mechanism underlying these effects, we have measured second virial coefficients (A2) of the heavily glycosylated pheniophora lycii phytase (Phy) and its enzymatically deglycosylated counterpart (dgPhy) in native and in denatured form by means of small angle x-ray scattering. The measured A2-values show that the native forms of Phy and dgPhy are equally repulsive at the studied pH 8 where A2 equals 10.9 +/- 0.1 x 10(4) mL mol g(-2). However, when thermally denatured, the A2 of dgPhy decreases to 9.0 +/- 0.2 x 10(4) mL mol g(-2) whereas it remained unchanged for Phy. In accord with earlier investigations, the p(r)-function measured here suggested that the glycans did not affect the peptide structure of the native protein. Conversely, glycosylation markedly changed the structure of thermally denatured protein. This was evident from the radius of gyration, which increased by 32% for Phy and only 11% for dgPhy on denaturation. We suggest that this expanding effect of the glycans on the denatured protein conformation relies on steric hindrance that limits the range of torsion angles available to the polypeptide. | 18,835,893 |
No impact of protein phosphatases on connexin 43 phosphorylation in ischemic preconditioning. | Cardiac connexin 43 (Cx43) is involved in infarct propagation, and the uncoupling of Cx43-formed channels reduces infarct size. Cx43-formed channels open upon Cx43 dephosphorylation, and ischemic preconditioning (IP) prevents the ischemia-induced Cx43 dephosphorylation. In addition to the sarcolemma, Cx43 is also present in the cardiomyocyte mitochondria. We now examined the interaction of Cx43 with protein phosphatases PP1alpha, PP2Aalpha, and PP2Balpha and the role of such interaction for Cx43 phosphorylation in preconditioned myocardium. Infarct size (in %area at risk) in left ventricular anterior myocardium of Göttinger minipigs subjected to 90 min of low-flow ischemia and 120 min of reperfusion was 23.1 +/- 2.7 [n = 7, nonpreconditioned (NIP) group] and was reduced by IP to 10.0 +/- 3.2 (n = 6, P < 0.05). Mitochondrial and gap junctional Cx43 dephosphorylation increased after 85 min of ischemia in NIP myocardium, whereas Cx43 phosphorylation was preserved with IP. PP2Aalpha and PP1alpha, but not PP2Balpha, were detected by Western blot analysis in the left ventricular myocardium. Cx43 coprecipitated with PP2Aalpha but not with PP1alpha. Although the total PP2Aalpha immunoreactivity (confocal laser scan) was increased to 154 +/- 24% and 194 +/- 13% of baseline (P < 0.05) after 85 min of ischemia in NIP and IP myocardium, respectively, the PP2A activities were similar between the groups. The amount of PP2Aalpha coimmunoprecipitated with Cx43 remained unchanged. Only PP2Aalpha coprecipitates with Cx43 in pig myocardium. This interaction is not affected by IP, suggesting that PP2Aalpha is not involved in the prevention of the ischemia-induced Cx43 dephosphorylation by IP. | 18,835,920 |
Nerve stimulation induced overflow of neuropeptide Y and modulation by angiotensin II in spontaneously hypertensive rats. | The sympathetic nervous system and renin-angiotensin system are both thought to contribute to the development and maintenance of hypertension in experimental models such as the spontaneously hypertensive rat (SHR). We demonstrated that periarterial nerve stimulation (NS) increased the perfusion pressure (PP) and neuropeptide Y (NPY) overflow from perfused mesenteric arterial beds of SHRs at 4-6, 10-12, and 18-20 wk of age, which correspond to prehypertensive, developing hypertensive, and maintained hypertensive stages, respectively, in the SHR. NS also increased PP and NPY overflow from mesenteric beds of Wistar-Kyoto (WKY) normotensive rats. NS-induced increases in PP and NPY were greater in vessels obtained from SHRs of all three ages compared with WKY rats. ANG II produced a greater increase in PP in preparations taken from SHRs than WKY rats. ANG II also resulted in a greater increase in basal NPY overflow from 10- to 12-wk-old and 18- to 20-wk-old SHRs than age-matched WKY rats. ANG II enhanced the NS-induced overflow of NPY from SHR preparations more than WKY controls at all ages studied. The enhancement of NS-induced NPY overflow by ANG II was blocked by the AT1 receptor antagonist EMD-66684 and the angiotensin type 2 receptor antagonist PD-123319. In contrast, ANG II greatly enhanced norepinephrine overflow in the presence of PD-123319. Both captopril and EMD-66684 decreased neurotransmitter overflow from SHR mesenteric beds; therefore, we conclude that an endogenous renin-angiotensin system is active in this preparation. It is concluded that the ANG II-induced enhancement of sympathetic nerve stimulation may contribute to the development and maintenance of hypertension in the SHR. | 18,835,922 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.