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Remeasuring the double helix.
DNA is thought to behave as a stiff elastic rod with respect to the ubiquitous mechanical deformations inherent to its biology. To test this model at short DNA lengths, we measured the mean and variance of end-to-end length for a series of DNA double helices in solution, using small-angle x-ray scattering interference between gold nanocrystal labels. In the absence of applied tension, DNA is at least one order of magnitude softer than measured by single-molecule stretching experiments. Further, the data rule out the conventional elastic rod model. The variance in end-to-end length follows a quadratic dependence on the number of base pairs rather than the expected linear dependence, indicating that DNA stretching is cooperative over more than two turns of the DNA double helix. Our observations support the idea of long-range allosteric communication through DNA structure.
18,927,394
Influence of Campylobacter fetus subsp. fetus on ram sperm cell quality.
Campylobacter fetus subsp. fetus infection can occur in female sheep, causing infertility or abortion. Despite extensive research on the effect of these bacteria on female fertility, little research has been done on the influence of C. fetus subsp. fetus on the male factor. Our objective was to examine the influence of C. fetus subsp. fetus on ram sperm. Motility index, percentage of live spermatozoa, mean alphat value (an indication of the chromatin stability of the sperm cell) and percentage of sperm cells expressing the FAS receptor were measured in sperm incubated in the presence or absence of C. fetus subsp. fetus. The motility index and viability of sperm incubated with the bacteria were lower than those of untreated sperm samples after 5 h. In bacteria-incubated sperm cells, the percentage expressing FAS receptor was already significantly elevated at 15 min. Bacteria-incubated sperm showed a greater prevalence of morphological damage. The bacteria were attached to tail and acrosome regions, and the sperm damage was concentrated in both the motility and chromatin regions. Bacteria-infected sperm cells showed a decrease in motility, increase in early acrosome reaction and chromatin damage. Similar effects were induced by incubation of the sperm with supernatants from C. fetus subsp. fetus cultures. Thus this study demonstrates that C. fetus subsp. fetus has a detrimental effect on the quality of ram sperm.
18,927,420
Determinants of awareness, initiation and maintenance of physical activity among the over-fifties: a Delphi study.
To develop effective interventions to stimulate physical activity (PA), insight into its underlying variables is needed. The aim of this study was to obtain an overview of the most relevant determinants of awareness, initiation and maintenance of PA among the over-fifties by means of a three-round Delphi study. In the first round, 17 key-experts outlined possible relevant determinants into an open-ended electronic questionnaire. In the second round, 118 experts completed a structured electronic questionnaire that was based on the first round results, in which they scored each determinant on its relevance. In the third round, experts were asked to re-rate the relevance of each determinant, after feedback was given about the group median relevance score. After three rounds, the experts agreed on 30 relevant determinants of the three phases of PA. When compared with longitudinal studies, the Delphi study pointed out new concepts, such as several post-motivational and social and environmental determinants as possible relevant determinants, suggesting that this method has the potential to trace new and promising determinants. The results further showed that next to similarities, much dissimilarity in relevant determinants of awareness, initiation and maintenance of PA was found, suggesting that most determinants could be phase specific.
18,927,443
The political solidarity model of social change: dynamics of self-categorization in intergroup power relations.
Social and political change involves a challenge to the status quo in intergroup power relations. Traditionally, the social psychology of social change has focused on disadvantaged minority groups collectively challenging the decisions, actions, and policies of those in positions of established authority. In contrast, this article presents a political solidarity model of social change that explores the process by which members of the majority challenge the authority in solidarity with the minority. It is argued that political solidarity as a social change process involves a contest between the authority and the minority over the meaning of a shared (higher order) identity with the majority. When identity ceases to be shared with the authority and becomes shared with the minority, majority challenge to authority in solidarity with the minority becomes possible. The model's contributions to existing social psychological approaches to social change are also discussed.
18,927,471
Busulfan produces efficient human cell engraftment in NOD/LtSz-Scid IL2Rgamma(null) mice.
Xenografting immunodeficient mice after low-dose irradiation has been used as a surrogate human hematopoietic stem cell (HSC) assay; however, irradiation requires strict and meticulous animal support and can produce significant mortality rates, limiting the usefulness of this model. In this work, we examined the use of parenteral busulfan as an alternative conditioning agent. Busulfan led to dose-dependent human HSC engraftment in NOD/LtSz-scid/IL2Rgamma(null) mice, with marked improvement in survival rates. Terminally differentiated B and T lymphocytes made up most of the human CD45+ cells observed during the initial 5 weeks post-transplant when unselected cord blood (CB) products were infused, suggesting derivation from existing mature elements rather than HSCs. Beyond 5 weeks, CD34+-enriched products produced and sustained superior engraftment rates compared with unselected grafts (CB CD34+, 65.8% +/- 5.35%, vs. whole CB, 4.27% +/- 0.67%, at 24 weeks). CB CD34+ group achieved significantly higher levels of engraftment than mobilized CD34+-enriched peripheral blood (PB CD34+). At 8 weeks, all leukocyte subsets were detected, yet human red blood cells (RBCs) were not observed. Transfused human red cells persisted in the chimeric mice for up to 3 days; an accompanying rise in total bilirubin suggested hemolysis as a contributing factor to their clearance. Recipient mouse-derived human HSCs had the capacity to form erythroid colonies in vitro at various time points post-transplant in the presence of human transferrin (Tf). When human Tf was administered singly or in combination with anti-CD122 antibody and human cytokines, up to 0.1% human RBCs were detectable in the peripheral blood. This long evasive model should prove valuable for the study of human erythroid cells.
18,927,475
How much time does it take to get a pressure ulcer? Integrated evidence from human, animal, and in vitro studies.
Severe pressure ulcers and deep tissue injury are associated with higher mortality rates, longer hospital stays, and costly treatment. Time is a critical factor in commonly employed measures (eg, pressure redistribution for wheelchair users and patient turning schedules) to prevent pressure ulcers and deep tissue injury. Surprisingly, information regarding the timeframe for pressure ulcer onset, particularly for deep tissue injury onset, is scant. To create a timeframe for the development of pressure ulcers and deep tissue injury, available evidence from the following study types was obtained and reviewed: 1) studies involving patients who underwent surgeries of known duration and subsequently developed a serious pressure ulcer with subcutaneous tissue damage or deep tissue injury; 2) animal studies in which loads were applied on soft tissues of anesthetized animals and tissue viability monitored in real time or using histology post-euthanasia; and 3) in vitro models in cell cultures and tissue-engineered constructs. Findings from the three models indicate that pressure ulcers in subdermal tissues under bony prominences very likely occur between the first hour and 4 to 6 hours after sustained loading. However, research examining these timeframes in sitting patients is not available. Further fundamental research, employing animal and cell culture models, is required to narrow this range further and to correlate the time factor to the extent of tissue damage.
18,927,481
Evaluation of the antioxidant activity of Syzygium cumini leaves.
The antioxidant activity of Syzygium cumini leaf extracts was investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging and ferric-reducing antioxidant power (FRAP) assays. The methanolic extract and its four water, ethyl acetate, chloroform, and n-hexane fractions were prepared and subjected to antioxidant evaluation. The results showed that the ethyl acetate fraction had stronger antioxidant activity than the other ones. HPLC data indicated that S. cumini leaf extracts contained phenolic compounds, such as ferulic acid and catechin, responsible for their antioxidant activity. A significant linear relationship between antioxidant potency, free radical-scavenging ability and the content of phenolic compounds of leaf extracts supported this observation.
18,927,517
Recent synthetic approaches toward non-anomeric spiroketals in natural products.
Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect.
18,927,519
Inhibitory effect of antihypertensive drugs on calcineurin in cardiomyocytes.
In recent years, a handful of research investigations have shown that some antihypertensive drugs, i.e., angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB), can inhibit myocardial expression and/or activity of calcineurin. Calcineurin is a Ca(2+)-calmodulin-dependent serine/threonine phosphatase and is a target for some immunosuppressive drugs. It is well known that traditional immunosuppressants, such as cyclosporine A (CsA) and tacrolimus (FK506), are anticalcineurin, and their prohypertensive effects are such that antihypertensive therapy is often required in organ transplant recipients who receive these drugs. Therefore, the idea that ACEI, ARB, and CCBs are both antihypertensive and anticalcineurin seems paradoxical. This invited review tries to summarize these new findings and analyze the scientific and clinical significance of these claims. The review also emphasizes some of the shortcomings in these studies and some questions that need to be addressed in future investigations.
18,927,543
Ethnicity and weight status affect the accuracy of proxy indices of insulin sensitivity.
This study tested the hypotheses that correlations between direct measures of insulin sensitivity and proxy indices of insulin sensitivity derived from fasting values, (i) would not be affected by ethnicity, and (ii) would be stronger in overweight vs. weight-reduced states. We further hypothesized that associations between proxy indices and fat distribution would be similar to those between directly measured insulin sensitivity and fat distribution. Testing was performed in weight-stable conditions in 59 African-American (AA) and 62 white-American (WA) overweight, premenopausal women before and after a weight loss intervention. Subjects were retested 1 year following weight loss. Proxy indices were correlated against the insulin sensitivity index S(I) determined via minimal modeling. Fat distribution was assessed using computed tomography. Correlations between Si and proxy indices were consistently stronger among overweight women (r = 0.44-0.52) vs. weight-reduced women (r = 0.18-0.32), and among AA (r = 0.49-0.56, baseline; 0.24-0.36, weight-reduced) vs. WA (r = 0.38-0.46, baseline; 0.19-0.31, weight-reduced). Among subjects who regained >3 kg after 1 year, correlations between S(I) and proxy indices were similar to those observed at baseline, whereas correlations were weak among women who maintained their reduced body weight. S(I) and all proxy indices were similarly correlated with intra-abdominal adipose tissue (IAAT) at baseline, but not after weight loss. In conclusion, correlations between S(I) and proxy indices were affected by both ethnicity and weight status. If proxy indices are used in multiethnic populations, or in populations including both lean and overweight/obese subjects, data should be interpreted with caution.
18,927,554
Fluoride varnish reduces white spot lesions during orthodontic treatment.
This was a randomised controlled trial (RCT) set in a community dental practice. The test varnish was a commercially available product, Fluor Protector (Ivoclar Vivadent, Schaan, Liechtenstein), containing 0.1% fluoride as difluorosilane in a polyurethane varnish base. The placebo varnish applied had an identical composition but without fluoride. The incidence and prevalence of white spot lesions (WSL) on the upper incisors, cuspids and premolars were recorded, as scored from digital photographs by two independent examiners. In the case of disagreement, cases were re-examined until a consensus was achieved. The incidence of WSL during the treatment period was 7.4% in the fluoride varnish group compared with 25.3% placebo group (P <0.001). The mean progression score was significantly lower in the fluoride varnish group than in the placebo group, (0.8 +/- 2.0 vs 2.6 +/- 2.8; P <0.001). The absolute risk reduction was 18% and the number-needed-to-treat was calculated to be 5.5 (95% confidence interval, 3.7-10.9). The results strongly suggest that regular topical fluoride varnish applications may reduce the development of WSL adjacent to the bracket base during treatment with fixed appliances.
18,927,569
Do folic acid supplements reduce facial clefts?
This was a national population-based case-control study in Norway. CASE AND CONTROL SELECTION: Cases consisted of all newborn infants born from 1996-2001 who had been referred for surgical treatment of a cleft [either cleft lip with or without cleft palate (377 children) or cleft palate only (196 children)]. Controls (763) were a randomly selected at an average of four per 1000 live births (identified through the medical birth registry of Norway). Data were collected using questionnaires. Crude odds ratios (OR) were calculated and adjustments for potential confounders (diet and multivitamins, mother's education, mother's employment during early pregnancy, smoking, alcohol consumption, and year of baby's birth) were made. Folic acid supplementation during early pregnancy (400 microg/day) was associated with a reduced risk of isolated cleft lip with or without cleft palate after adjustment for multivitamins, smoking, and other potential confounding factors [adjusted OR, 0.61; 95% confidence interval (CI), 0.39-0.96]. Independent of supplements, diets rich in fruits, vegetables and other high-folate-containing foods reduced the risk somewhat (adjusted OR, 0.75; 95% CI, 0.50-1.11). The lowest risk of cleft lip was among women who ate folate-rich diets who also took folic acid supplements and multivitamins (adjusted OR, 0.36; 95% CI, 0.17-0.77). Folic acid provided no protection against cleft palate alone (adjusted OR, 1.07; 95% CI, 0.56-2.03). Folic acid supplements during early pregnancy seem to reduce the risk of isolated cleft lip (with or without cleft palate) by about a third. Other vitamins and dietary factors may provide additional benefit.
18,927,570
Handsearching still a valuable element of the systematic review.
The Cochrane Methodology Register, Medline, Embase, AMED, Biosis, Cinahl, LISA, and Psycinfo were consulted along with researchers who may have carried out relevant studies. Studies were considered eligible if they compared searching by hand with searching one or more electronic databases to identify reports of randomised trials. The main outcome measure was the number of reports of randomised trials identified from searches made by hand compared with electronic searching. Data were extracted regarding the electronic database searched, the complexity of electronic search strategy used, the characteristics of the journal reports identified, and the type of trial report identified. Thirty-four studies were included. Handsearching identified between 92 and 100% of the total number of reports of randomised trials found in the various comparisons in this review. Searching Medline retrieved 55%, Embase 49% and Psycinfo 67%. The retrieval rate of the electronic database varied depending on the complexity of the search. The Cochrane highly sensitive search strategy (HSSS) identified 80% of the total number of reports of randomised trials found; searches categorised as 'complex' (including the Cochrane HSSS) found 65% and 'simple' searches found 42%. The retrieval rate for an electronic search was higher when the search was restricted to English-language journals, at 62% versus 39% for journals published in languages other than English. When the search was restricted to full reports of randomised trials, the retrieval rate for an electronic search improved: a complex search strategy retrieved 82% of the total number of such reports of randomised trials. Hand searching is still valuable in identifying randomised trials for inclusion in systematic reviews of healthcare, particularly trials reported as abstracts or letters, those published in languages other than English, along with all reports published in journals not indexed in electronic databases. Where time and resources are limited, however, searching an electronic database using a complex search (or the Cochrane HSSS) will identify the majority of trials published as full reports in English language journals, provided, of course, that the relevant journals have been indexed in the database.
18,927,572
Epigenome dynamics: a quantitative genetics perspective.
Classically, quantitative geneticists have envisioned DNA sequence variants as the only source of heritable phenotypes. This view should be revised in light of accumulating evidence for widespread epigenetic variation in natural and experimental populations. Here we argue that it is timely to consider novel experimental strategies and analysis models to capture the potentially dynamic interplay between chromatin and DNA sequence factors in complex traits.
18,927,581
Comparison of higher order aberrations in eyes with aspherical or spherical intraocular lenses.
To compare ocular, internal, corneal aberrations, and contrast sensitivity in patients implanted with aspheric or spherical intraocular lenses (IOLs). Total, corneal, and internal aberrations were measured using ray-tracing technology in 23 eyes implanted with aspheric (Tecnis ZA9003) IOLs, and in 25 eyes implanted with spherical (AcrySof SA60AT) IOLs. Spherical aberration (SA), coma, trefoil, and RMS of higher order aberrations (HOAs) were analysed for 4.0 and 6.0 mm optical zones. Best-corrected visual acuities (BCVAs), contrast sensitivity under photopic and mesopic conditions, and modulation transfer function (MTF) were evaluated to compare visual performances. The mean internal SA was -0.06/-0.35 microm in the aspheric IOL group and 0.04/0.17 microm in the spherical IOL group (at 4 mm/6 mm pupil). Total SA was near to zero in the aspheric IOL group, and was 0.11+/-0.034/0.48+/-0.13 microm in the spherical IOL group. The internal Z(3)(-1) and total Z(3)(-1) were more negative in the spherical IOL group. The internal Z(3)(-3) was more negative in the aspheric IOL group. The two groups were similar in terms of other Zernike values and RMS of HOA. There were no differences in BCVA between groups. The aspheric IOL group showed better contrast sensitivity at 3-6 cpd in photopic and 1.5-6 cpd in mesopic conditions. The MTF curve was better for the aspheric IOL group at 5-10 cpd. The aspheric IOL with a negative SA reduced total SA by compensating for positive corneal SA. These effects resulted in improved contrast sensitivity.
18,927,594
Signaling flux redistribution at toll-like receptor pathway junctions.
Various receptors on cell surface recognize specific extracellular molecules and trigger signal transduction altering gene expression in the nucleus. Gain or loss-of-function mutations of one molecule have shown to affect alternative signaling pathways with a poorly understood mechanism. In Toll-like receptor (TLR) 4 signaling, which branches into MyD88- and TRAM-dependent pathways upon lipopolysaccharide (LPS) stimulation, we investigated the gain or loss-of-function mutations of MyD88. We predict, using a computational model built on the perturbation-response approach and the law of mass conservation, that removal and addition of MyD88 in TLR4 activation, enhances and impairs, respectively, the alternative TRAM-dependent pathway through signaling flux redistribution (SFR) at pathway branches. To verify SFR, we treated MyD88-deficient macrophages with LPS and observed enhancement of TRAM-dependent pathway based on increased IRF3 phosphorylation and induction of Cxcl10 and Ifit2. Furthermore, increasing the amount of MyD88 in cultured cells showed decreased TRAM binding to TLR4. Investigating another TLR4 pathway junction, from TRIF to TRAF6, RIP1 and TBK1, the removal of MyD88-dependent TRAF6 increased expression of TRAM-dependent Cxcl10 and Ifit2. Thus, we demonstrate that SFR is a novel mechanism for enhanced activation of alternative pathways when molecules at pathway junctions are removed. Our data suggest that SFR may enlighten hitherto unexplainable intracellular signaling alterations in genetic diseases where gain or loss-of-function mutations are observed.
18,927,610
Shoulder dystocia: what is the risk of recurrence?
To study the recurrence risk of shoulder dystocia in women who have previously experienced at least once shoulder dystocia. A retrospective study of vaginal deliveries complicated by shoulder dystocia. Setting. American University of Beirut Medical Center - Lebanon. Vaginal deliveries complicated by shoulder dystocia over a 15-year period who had subsequent vaginal delivery. Methods. Charts of index and subsequent deliveries beyond 24 weeks' gestation were reviewed for demographics and intrapartum events. Women were divided into those with recurrent shoulder dystocia (group I) and those with uncomplicated subsequent delivery (group II) and compared. Recurrent shoulder dystocia and characteristics of women with recurrence. The incidence of shoulder dystocia was 0.9% of all vaginal deliveries. Of 193 shoulder dystocia cases, 48 women had a subsequent delivery. After excluding cesarean deliveries (n=4), 44 women were analyzed. Eleven had recurrent shoulder dystocia (25.0%). Mean birthweight was larger (4,019+/-430 vs. 3,599+/-398 g, p=0.005) with a higher rate of macrosomia > or =4,000 g (63.6 vs. 15.2%, p=0.004) and the birthweight in the subsequent pregnancy was larger than the index pregnancy in a significantly larger proportion of women in group I compared with group II (72.7% vs. 33.3%, p=0.035). Otherwise, maternal age, gestational age at delivery, parity, duration of labor, gender, history of macrosomia, and interval between pregnancies were similar. The risk of recurrence of shoulder dystocia is around 25%. When counseling women about recurrence risk, the absence of macrosomia and a smaller birthweight than the previous pregnancy could be reassuring.
18,927,947
[Vascular pathology in first-degree relatives of patients with intracranial aneurysms].
An aim of the study was to compare by the analysis of pedigrees the frequency of vascular pathology in first-degree relatives (FDR) of patients with intracranial aneurysms (IA) and controls. Pedigrees were selected by interviewing 194 patients with IA (94 men and 100 women) and 193 age- and sex-matched control patients. Only FDR with complete information about their health status were included: 1011 FDR of patients with IA and 812 FDR of controls. The results of the study revealed that the frequency of strokes was 2.5 times higher in FDR of patients with IA than in those of controls: 6.5% and 2.6%, respectively (RR = 2.52, 95% CI = 1.56-4.09). Hemorrhages occurred 3.7 times more often in FDR of patients with IA than in FDR of controls: 3.4% versus 0.9% (RR = 3.90, 95% CI = 1.74-8.75). Only 0.9% of FDR of patients with IA had the rupture of intracranial aneurysm compared with nobody in FDR of controls. The frequency of headaches was 2.8 times greater in FDR of patients with IA than in those of controls: 19.6% versus 7.1% (RR = 2.74, 95% CI = 2.08-3.62). FDR of patients with IA suffered from arterial hypertension 2 times more often than FDR of controls: 24.9% and 11.6%, respectively (RR = 2.15, 95% CI = 1.73-2.68). Coronary heart disease was 2.7 times more frequent in FDR of patients with IA than in controls: 8.9% and 3.3%, respectively (RR = 2.68, 95% CI = 1.76-4.07). Sudden death occurred in FDR of patients with IA 5.8 times more often than FDR of controls: 11.1% and 1.9%, respectively (RR = 5.68, 95% CI = 1.37-23.39). Thus, vascular pathology occurs relatively often in FDR of patients with IA implying that vascular defects which cause the development of IA may be, at least in part, genetically determined. Prevention of stroke and cardiovascular disease is necessary for FDR of patients with IA.
18,927,979
Advances in endoscopic sinonasal and anterior skull base surgery.
Endoscopic transnasal surgery is rapidly replacing more radical external 'open' procedures. At Groote Schuur Hospital, Cape Town, we performed 94 advanced endoscopic sinonasal and anterior skull base procedures over a 2-year period. Most of these would previously have been performed using large external incisions requiring more invasive surgery with significantly higher morbidity. Endoscopic surgery is more cost-effective than open procedures because it reduces duration of hospitalisation, operating time and theatre consumables and obviates the need for postoperative intensive care unit admission. We have had no complications other than 2 cerebrospinal fluid leaks, but the potential risks of endoscopic sinonasal and skull base surgery are significant and proper training is required.
18,928,042
County government resources associated with dependent-adult abuse investigations in Iowa.
This study evaluated on a county level the association of Iowa's domestic dependent-adult abuse investigations with the location of adult protective services (APS) offices, rurality, government resources, felony charges and prosecutions, child abuse reports, and census demographics. In 2003, the rate of dependent-adult abuse investigations for Iowa was 0.70 per 1,000 population age 18 and older. Higher rates of child abuse investigations, felony prosecutions, sheriff's annual salary, and lower rates of child abuse substantiations are associated with higher rates of dependent-adult abuse investigations and substantiations.
18,928,053
Control of blood-transmitted infections in dentistry.
As knowledge has accumulated on the blood-transmitted pathogenic agents, the contact with biological fluids (blood, plasma, saliva, etc.) from apparently healthy individuals has started to be regarded as a real professional risk for dentists. Theoretically, exposure to a contaminated biological specimen may have as a consequence transmission of infection from patient to dentist, from dentist to patient and from patient to patient via inadequately decontaminated and sterilized dental equipment. The present study is concerned with the analysis of the specific conditions that favor the occurrence of the epidemic process, the estimation of the risk degree of transmission of infections caused by hepatitis B, C viruses as well as of HIV infection in Romania. The data for the study were collected using two processes. First a self reporting survey and secondly an experimental procedure were performed. The testing of dentists' knowledge of blood transmissible diseases and infection control in their offices were performed using a questionnaire with 129 questions. The professional incidents/accidents representing a potential risk were counted using a questionnaire (with 37 questions). Serological markers were tested with ELISA kits. The monitoring of sterilization was accomplished with a questionnaire and biological tests. Many conclusions result from the study. There is an extremely reduced probability and infection transmission from the dentist to the patient. The transmission of infection from the patient to the dentist represents a low risk (for all that, the risk should not be minimized). The rigorous control and observation of infection prevention measures in dental offices is necessary to stop the infection transmission from patient to patient. The dentists' postgraduate training in infection control measures should be completed with knowledge regarding the blood transmissible infections epidemiology. Learning more about the epidemiological process enables the dentists to avoid wrong attitudes and behaviors.
18,928,060
Virulence characteristics of Escherichia coli isolates from children with urinary tract infections.
The urinary tract is among the most common sites of bacterial infection and E. coli is by far the most common infecting agent in children and adults of both sexes. In an attempt to evaluate the intrinsic virulence of E. coli uroisolates from children, 54 strains were assessed by using PCR for the presence of five representative genetic determinants coding for adherence systems (pap, sfa/foc, afa), and toxins (hly and cnf). The prevalence of pap, sfa/foc and afa genes was 55%, 54%, and 44%, respectively. Hemolysin-encoding gene hly was detected in 55% strains, while cnf was exhibited by 35% of the screened E. coli isolates. Among the 39 PCR positive strains isolated from children's urine cultures the co-occurrence of the various targeted virulence genes was detected in 30 strains, the virulence profiles identified suggesting the presence of their localization on chromosomal regions known as pathogencity-associated islands. The rapid and reliable detection of the intrinsic virulence potential by this molecular approach could be very useful when evaluating the importance of microorganism pathogenicity versus host's susceptibility for developing an overt symptomatology of infection.
18,928,062
Fungal control of pathogenic fungi isolated from wild plants in Taif Governorate, Saudia Arabia.
Twenty two plants were collected from Taif Governorate and identified as: Euphorbia glomerifera, Juniperus procera, Launaea mucronata, Capparis dcidua, Punica granatum, Opuntia ficus, Prunus persica, Eucalyptus globulus, Medicago sativa, Artemisia monosperma, Trichodesma calathiforme, Artemisia judaica, Foeniculum vulgare, Phagnalon sinaicum, Rumex dentatus, Asphodelus aestives, Pulicaria crispa, Launae sonchoides, Forsskaolea tenacissima, Arnebia hispidissima, Avena spp and Aerva lanata. Pathogenic fungi were isolated from some of these plants and identified as Alternaria alternate, Ulocladium botrytis, Cladosporium spp, Cephalosporium spp, Penicillium chrysogenum, Fusarium oxysporum and Humicola grisea. Four antagonistic isolates were tested, 2 from Gliocladium fungus and 2 from Trichoderma fungus. We found that all the four antagonistic isolates (G. deliquescens, G. virens, T. viride and T. hamatum) significantly inhibited the radial growth of the pathogenic fungi tested, with different ratios. The results indicated that the antibiotics produced by the antagonists were more effective than the fungus itself and differ with different fungi. Coating plant stems with antagonists or with antagonist extracts reduce the severity of the disease but not prevent it in all tested pathogens.
18,928,069
Histomorphometric characteristics of peritoneal blood microvessels.
We assessed histological characteristics and sex related differences in morphometric parameters of healthy persons' peritoneal blood vessels. Eighteen samples of parietal peritoneum were collected from 11 healthy persons with elective abdominal surgery, 6 males and 5 females, age range 44-58. Tissue samples were prepared for light and transmission electron microscopy. Morphometric parameters of peritoneal blood vessels were determined by analySIS 3.1 Soft Imaging System GMbH. We directly measured outer and lumen diameter, and outer and lumen surface on blood vessels transversal sections. Wall thickness, lumen diameter-wall thickness ratio, blood vessels numerical density and peritoneal tissue surface under blood vessels were calculated subsequently. Results were statistically analysed with Student T test. Mostly true and venous capillaries were observed. Endothelial citoplasm showed numerous mitochondria, ribosomes and pinocytotic vesicles, prominent rough endoplasmic reticulum, well-developed Golgi complex, and predominantly euchromatic nuclei. No statistically significant differences were found between male and female subjects in any of the investigated variables, rphometric characteristics of pelvic peritoneal blood vessels did not show gender related differences.
18,928,159
Renal Doppler ultrasound in patients with hypertension and metabolic syndrom.
Evaluation of the renal changes by conventional and Doppler ultrasound (US) was performed in patients with hypertension and obesity. 67 persons were examined and divided in 3 groups. Group I includes 27 patients--15 M and 12 F, average age 52+/-4.87 with well controlled diabetes mellitus type II and hypertension, Ccr.--139+/-1.31. Group II includes 20 patients--9 M and 11 F, average age 53+/-7 with well controlled hypertension without diabetes, with Ccr 128+/-7.8. Group III--20) pts. 8 F and 12 M, average age 54+/-5 with uncontrolled hypertension without diabetes, with Ccr 128+/-7.8. All examined pts. were with BMI>30 and hyperlipidemia--total cholesterol>6.5 mmol/l. Tests for microalbuminuria were negative in all 3 groups. In all three groups, using conventional US, the following parameters were detected by Aloca 4000 machine: renal (RV) and parenchyma (PV) volumes as well as Doppler parameters RI, PI, Vmax, Vmin, and Vmean. There were no significant differences between RV and PV of all examined groups: Group I--254+/-53, Group II--238+/-38, Group III--263+/-38, p=0.1. The strong correlation between renal volumes and BMI was found (Pearson's r 0.58). There were no significant differences between Vmax, Vmin, Vmean in all three groups. RI is normal <0.7 in all examined patients: Group I--0.63+/-0.06, Group II--0.61+/-0.02, Group III--0.66+/-0.03. RI in group III was significantly higher, p<0.05 compared to RI indices detected in other two groups but remains at normal levels. Intrarenal hemodynamics exhibited no difference in all examined groups. Analysis of the Doppler spectrum of the intrarenal arteries provides an accurate information about renal vascular changes but has no significant advantages in patients with hypertension and obesity with normal renal function and signs of hypertensive nephropathy "benign nephrosclerosis". Nevertheless Duplex Doppler Ultrasound is a noninvasive method which is an important part of the diagnostic algorithm in patients with diseases characterized by vascular involvement such as hypertension.
18,928,166
[Frequency of polyneuropathy signs in CAPD patients].
It is well known that polyneuropathy has been an important cause of disability in patients maintained on hemodialysis as well as on peritoneal dialysis. The present study was aimed to analyze frequency and causes of polyneuropathy in patients on continuous ambulatory peritoneal dialysis (CAPD). Sixty three CAPD patients (37 men), aged between 30 and 85 who were on dialysis from 1 to 290 months, were analyzed. Biochemical parameters and dialysis adequacy (KT/V) were determined. Motor conduction velocity (MCV) of peroneal and tibial nerve, and sensitive conduction velocity (SCV) on sural nerve were measured. Biochemical parameters and dialysis adequacy were satisfactory in patients on CAPD. Polyneuropathy symptoms like paresthesias, pain, cramps and disability were found in more than 50% of patients. Over 80% of analyzed patients had pathological neurophysiological parameters: latency of F wave of n. peroneus and all analyzed parameters of n. tibialis, as the well as SCV on the sural nerve. A significant correlation was found between peroneal MCV and age, glycemia and serum creatinine; peroneal terminal latency (TL) and age; peroneal F wave and glycemia and serum urea; tibial MCV and glycemia; tibial F wave and glycemia, serum urea and KT/V. The most frequent signs of uremic polyneuropathy are reduced SCV on sural nerve and prolonged latency of F wave on peroneal and tibial nerves. Neurophysiological parameters on the lower extremities in patients on CAPD are in correlation with dialysis adequacy, glycemia and age.
18,928,181
[Left ventricular hypertrophy in patients on hemodialysis: importance of anemia].
Cardiovascular diseases are the most frequent cause of mortality in hemodialysis patients. Left ventricular hypertrophy is the main risk factor for development of cardiovascular morbidity and mortality in patients on hemodialysis. Anemia is the only main risk factor for the development of left ventricular hypertrophy in patients on hemodialysis. The aim of this study was to examine the impact of anemia in the development of left ventricular hypertrophy, and correlation between anemia and echocardiographic parameters for the assessment of left ventricular hypertrophy. The research was conducted on 115 patients (M:F 71:44) regularly treated by hemodialysis, average age 53.30+/-1.2.17 years, average length of dialysis 4.51+/-4.01 years and average Kt/Vsp index 1.17+/-0.23. Depending on the level of hemoglobin, the patients were divided into three groups. The basic parameters investigated were the following: hemoglobin, hematocrite, serum concentrations of albumin, CRP, total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride serum concentrations, parathormon, diastolic thickness of interventricular septu-mIVSd, diastolic thickness of left ventricular posterior wall, relative wall thickness-RWT, left ventricular mass index-LVMi, index of left ventricular end-diastolic volume-iLVEDV. The results were statistically analyzed using ANOVA, Kruskal-Wallis test, Student t-test, Mann-Whitney U test, Univariate logistic regression analysis test, and Multivariate logistic regression analysis test. The patients with hemoglobin <80 g/l had a very significantly higher (p<0.01), while the patients with hemoglobin 80-100 g/l had a significantly higher (p<0.05) left ventricular mass index than patients with hemoglobin >100 g/l. The univariate logistic regression analysis has showed that lower HDL cholesterol, anemia, higher systolic arterial pressure and higher mean arterial pressure cumulatively lead to the development of left ventricular hypertrophy. Multivariate logistic regression analysis established anemia as an independent risk factor for the development of left ventricular hypertrophy. Anemia is an independent risk factor for the development left ventricular hypertrophy. Identification of patients with increased risk for development of left ventricular hypertrophy and application of appropriate therapy to attain target values of risk factors, result in the regression of left ventricular hypertrophy, reduced cardiovascular morbidity and mortality rates and improved quality of life in patients treated with regular hemodialyses.
18,928,184
Bioinformatics databases and tools in virology research: an overview.
Viruses are major factors of human infectious diseases. Understanding of the structure-function correlation in viruses is important for the identification of potential anti-viral inhibitors and vaccine targets. In virology research, virus-related databases and bioinformatic analysis tools are essential for discerning relationships within complex datasets about viruses and host-virus interactions. Bioinformatic analyses on viruses include the identification of open reading frames, gene prediction, homology searching, sequence alignment, and motif and epitope recognition. The predictions of features such as transmembrane domains, glycosylation sites, and protein secondary and tertiary structure are important for analyzing the structure-function relationship of proteins encoded in viral genomes. Biochemical pathway analysis can help elucidate information at the biological systems level. Microarray analysis provides methods for high throughput screening and gene expression profiling. Virus-related bioinformatics databases include those concerned with viral sequences, taxonomy, homologous protein families, structures, or dedicated to specific viruses such as influenza and herpes simplex virus (HSV). This review provides a guide and overview of computational programs for these analyses as a resource for genomics and proteomics studies in virology research. These resources are useful for understanding viral diseases, as well as for the design and development of anti-viral agents.
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Vector-G: multi-modular SVM-based heterotrimeric G protein prediction.
Heterotrimeric G proteins interact with G protein-coupled receptors in response to stimulation by hormones, neurotransmitters, chemokines, and sensory signals to intracellular signaling cascades. Recently reported studies indicate that G protein subunits play a significant role in different eukaryotic diseases including inflammation, neurological diseases, cardiovascular diseases, endocrine disorders as well as plant pathogen response, infectious hyphae growth, differentiation and virulence of pathogenic fungi. Thus a study of their functions, signaling pathways, and protein interactions may lead to the development of various preventive approaches. The diversity of alpha, beta and gamma subunits of G proteins necessitates a prediction algorithm that helps in the identification of new proteins such as Gbeta where WD-40 repeats are not well characterized. The currently available techniques for finding G proteins are homology based search analyses and wet lab experiments, which are not very effective in finding new classes of proteins. We present here a robust computational method for finding new G proteins and their homologs using a SVM based pattern recognition algorithm. Several physicochemical and compositional properties including dipeptide, tripeptide and hydrophobicity composition are used for generating the SVM classifiers. This method has 96.17%, 95.38%, 97.6% sensitivity and 99.45%, 100%, 100% specificity on test sets for G protein alpha, beta, and gamma subunits, respectively. This algorithm correctly predicts the known alpha, beta and gamma subunits reported in literature. One important contribution of this algorithm is that it helps in improving genome annotation of several proteins as G proteins and serves as a useful tool for comparative genomic analysis of G proteins. Using this method, novel G protein subunits are predicted in 31 genomes covering plant, fungi and animal kingdom. The software is available at the website http://biomine.cs.uah.edu/bioinformatics/svm_prog/scripts/GProteins/vectorg.html. Supplementary files: The supplementary files are available on http://www.bioinfo.de/isb/2008/08/0013/supplementary_ material/.
18,928,202
Elder abuse: the Canadian experience.
Abuse and neglect of older adults occurs in all Canadian communities and solutions require the coordinated efforts of society at large. Amelioration entails more than a legislative approach. Prevention of this growing problem is a social responsibility that requires networking and collaboration between different disciplines in all sectors of the community. This article will discuss elder abuse in Canada from a historical perspective, as well as current legislation, model programs, and research initiatives. It is intended to allow for comparison from the various countries presented in this volume. Hopefully, readers will find some models, or ideas, they may wish to explore or even replicate within their own jurisdictions.
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Mitomycin protection of peridural fibrosis in lumbar disc surgery.
In this prospective, randomized clinical study the authors sought to evaluate the effects of locally applied mitomycin C on peridural fibrosis during lumbar microdiscectomy. Patients undergoing lumbar disc surgery were randomly divided into 2 groups. Thirty patients had 1 mg/ml mitomycin C applied at the site of discectomy for 5 minutes, and 30 age- and sex-matched patients underwent lumbar microdiscectomy without mitomycin C application as the control group. The groups were compared for degree of postoperative neurological function, radicular/back pain, and degree of peridural fibrosis on MR imaging 6 months after the operation. The median follow-up was 18 months. No serious drug adverse effects and no clinically significant laboratory adverse effects were reported in patients in the mitomycin C group. Patients in both groups showed similar clinical recoveries postoperatively. On postoperative evaluation of the MR images, pain scores, and neurological function, patients given mitomycin C have shown no reduction of peridural fibrosis either clinically or radiographically. Mitomycin C is easy to use and safe in patients undergoing lumbar microdiscectomy. However, no benefit was observed either clinically or radiographically in this study.
18,928,218
Unilateral atlantal mass hypertrophy in acromegaly. Case report.
The authors report an extremely rare case of a patient with acromegaly who had unilateral enlargement of an atlas facet resulting in cord compression and progressive quadriparesis. Although unilateral atlas facet enlargement has been identified in the literature in cases of spondylosis and as a component of congenital malformation, its association with acromegaly has not previously been reported. Resection of the offending facetal bone and atlantoaxial fixation resulted in rapid neurological recovery.
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Magnetic resonance imaging versus histological assessment for estimation of lesion volume after experimental spinal cord injury. Laboratory investigation.
The purpose of this study was to compare measures of lesion volume obtained by means of 1.5-T MR imaging to those obtained by the Cavalieri method, 6 weeks after experimental spinal cord injury. Nine male Wistar rats were subjected to spinal cord injury by clip compression (50 g) at the T-4 level. Six weeks postinjury, the rats were sacrificed, and spinal cords were analyzed ex vivo for lesion volume by means of 1.5-T MR imaging and subsequently, by the Cavalieri method. In the latter method, cords were cut longitudinally in 25-microm sections and stained with solochrome cyanin for myelin. The area of the lesion was determined for each serial section, and the distance-weighted sum of all area measures was then calculated to estimate the total lesion volume. Bland-Altman analysis showed that the 2 methods had an acceptable level of agreement for lesion volume estimation, but the Cavalieri method was prone to an overestimation bias. The MR imaging estimates of lesion volume were greater than the Cavalieri method estimates in 3 spinal cords, but the difference between measures was within 1 standard deviation of perfect agreement in these 3 lesions, and the mean difference between measures was 18.3%. In contrast, in those lesions in which the Cavalieri method yielded larger lesion volumes (5 lesions), the difference between measures was 2 standard deviations away from perfect agreement for 2 animals and the mean difference between measures was 72.4%. The results illustrate that the overestimation bias of the Cavalieri method is due, in part, to artifacts produced during processing of the spinal cord tissue.
18,928,229
Structural characterization of a novel sulfated menaquinone produced by stf3 from Mycobacterium tuberculosis.
Mycobacterium tuberculosis, the causative agent of tuberculosis, produces unique sulfated metabolites associated with virulence. One such metabolite from M. tuberculosis lipid extracts, S881, has been shown to negatively regulate the virulence of M. tuberculosis in mouse infection studies, and its cell-surface localization suggests a role in modulating host-pathogen interactions. However, a detailed structural analysis of S881 has remained elusive. Here we use high-resolution, high-mass-accuracy, and tandem mass spectrometry to characterize the structure of S881. Exact mass measurements showed that S881 is highly unsaturated, tandem mass spectrometry indicated a polyisoprene-derived structure, and characterization of synthetic structural analogs confirmed that S881 is a previously undescribed sulfated derivative of dihydromenaquinone-9, the primary quinol electron carrier in M. tuberculosis. To our knowledge, this is the first example of a sulfated menaquinone produced in any prokaryote. Together with previous studies, these findings suggest that this redox cofactor may play a role in mycobacterial pathogenesis.
18,928,249
Nickel-catalyzed reductive carboxylation of styrenes using CO2.
A nickel-catalyzed reductive carboxylation of styrenes using CO2 has been developed. The reaction proceeds under mild conditions using diethylzinc as the reductant. Preliminary data suggests the mechanism involves two discrete nickel-mediated catalytic cycles, the first involving a catalyzed hydrozincation of the alkene followed by a second, slower nickel-catalyzed carboxylation of the in situ formed organozinc reagent. Importantly, the catalyst system is very robust and will fixate CO2 in good yield even if exposed to only an equimolar amount introduced into the headspace above the reaction.
18,928,253
Extending pummerer reaction chemistry. Application to the total synthesis of (+/-)-dibromoagelaspongin.
The sponge metabolite dibromoagelaspongin was synthesized in 16 steps from imidazole. The route features two successive oxidative cyclizations with complete control of regiochemistry to deliver the unusual triaminomethane core of the target. These oxidative cyclizations likely resulted from Pummerer-like processes on the imidazole-2-sulfoxide (sulfide) precursors.
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Impact of food disinfection on beneficial biothiol contents in strawberry.
In this study, the impact of four food disinfectants including hydrogen peroxide, free chlorine, and gaseous- and aqueous-phase ozone with industrial doses on the concentration of biothiol compounds gamma-glutamylcysteinylglycine (GSH) and cystein (CYS) in strawberry was investigated for 1, 5, 15, 30, and 60 or 120 min. Additionally, the amount of oxidized glutathione (GSSG) was analyzed for calculation of the GSH/GSSG ratio as an indicator of oxidative stress. After this treatment, thiol contents of strawberry samples were examined using high-performance liquid chromatography (HPLC) technique. According to the results of measurements, free chlorine treatment for only 60 min significantly decreased CYS content in strawberry (p < 0.05). A significant decline in the GSH/GSSG ratio was also observed when H2O2 was applied for all time intervals except for 1 min (p < 0.05). However, aqueous-phase ozone treatment did not significantly affect the thiol levels (p < 0.05). In conclusion, this study may provide optimum disinfection methods for strawberry to minimize loss of beneficial biothiols.
18,928,295
Interactions between beta-lactoglobulin and aroma compounds: different binding behaviors as a function of ligand structure.
Interactions between beta-lactoglobulin (BLG) in its monomeric form and a wide range of aroma compounds were investigated by Fourier transform infrared (FT-IR) and 2D nuclear magnetic resonance (NMR) spectroscopies. A screening of the ligands was carried out by FT-IR through the amide I region changes of BLG upon binding. The location of two binding sites was determined by 2D NMR from the study of 10 selected ligands with different structures. All of the data suggest at least two binding behaviors as a function of the chemical class, the hydrophobicity, or the structure of the ligands. The binding of the elongated aroma compounds, such as 2-nonanone or ethyl pentanoate, within the central cavity involves residues located at the entrance of the calyx and Trp19. The binding onto the protein surface of aroma compounds that have or adopt a compact structure occurs in a site located between strand beta-G, alpha helix, and strand beta-I.
18,928,299
Isotope exchange at equilibrium indicates a steady state ordered kinetic mechanism for human sulfotransferase.
Cytosolic sulfotransferase (SULT)-catalyzed sulfation regulates biosignaling molecular biological activities and detoxifies hydroxyl-containing xenobiotics. The universal sulfuryl group donor for SULTcatalyzed sulfation is adenosine 3'-phosphate 5'-phosphosulfate (PAPS). The reaction products are a sulfated product and adenosine 3',5'-diphosphate (PAP). Although the kinetics has been reported since the 1980s,SULT-catalyzed reaction mechanisms remain unclear. Human SULT1A1 catalyzes the sulfation of xenobiotic phenols and has very broad substrate specificity. It has been recognized as one of the most important phase II drug-metabolizing enzymes. Understanding the kinetic mechanism of this isoform is important in understanding drug metabolism and xenobiotic detoxification. In this report, we investigated the SULT1A1-catalyzed phenol sulfation mechanism. The SULT1A1-catalyzed reaction was brought to equilibrium by varying substrate (1-naphthol) and PAPS initial concentrations. Equilibrium constants were determined. Two isotopic exchanges at equilibrium ([14C]1-naphthol <=>[14C]1-naphthyl sulfate and[35S]PAPS<=>[35S]1-naphthyl sulfate) were conducted. First-order kinetics, observed for all the is otopic exchange reactions studied over the entire time scale that was monitored, indicates that the system was truly at equilibrium prior to addition of an isotopic pulse. Complete suppression of the 35S isotopic exchange rate was observed with an increase in the levels of 1-naphthol and 1-naphthyl sulfate in a constant ratio,while no suppression of the 14C exchange rate was observed with an increase in the levels of PAPS and PAP in a constant ratio. Data are consistent with a steady state ordered kinetic mechanism with PAPS and PAP binding to the free enzyme.
18,928,301
A novel ferroceneylazobenzene self-assembled monolayer on an ITO electrode: photochemical and electrochemical behaviors.
A novel ferroceneylazobenzene self-assembled monolayer (SAM) has been constructed on an indium-tin oxide (ITO) electrode via the covalent attachment of 4-(4'-11-ferrocenyl-undecanoxyphenylazo)benzoic acid ( FcAzCOOH) onto a silanized ITO substrate surface and verified by reflectance infrared spectroscopy and water contact angle. Atomic force microscopy (AFM) and cyclic voltammogram (CV) indicated that the FcAzCOOH formed a uniform and reproducible SAM on the ITO electrode with a surface coverage of ca. 1.9 x 10 (-10) mol/cm (2) (87 A (2)/molecule). The reversible photoisomerization behavior of the SAM was characterized by UV-vis spectra. The azo pi-pi* transition band intensity of the SAM gradually decreased with UV (365 nm) irradiation and was almost recovered again when subsequent exposure to ambient room light (400-800 nm). The increased tilt angle of the molecules on the ITO substrate after UV irradiation further confirmed the trans-to- cis isomerization of azobenzene moieties. The CV of the trans- FcAzCOOH modified ITO electrode showed a pair of waves due to redox of the ferrocene groups in the potential range of 0 to +800 mV (vs SCE), and the peak separation of the redox wave became larger after UV irradiation and almost returned to its original value after subsequent exposure to the visible light. Rate-dependent CV curves indicated that the charge transfer rate between the ferrocene species in the SAM and the ITO electrode was slowed down after UV irradiation due to the smaller porosity of the monolayer film and the more compact barrier layer between the redox species and the ITO electrode. It is the first time to directly observe the influence of photoisomerization of the azobenzene moiety on the redox behavior of redox species in the ferroceneylazobenzene-functionalized SAM. The present results provide profound insight into the role of redox microenvironment on electron transfer kinetics and also provide a simple and facile approach to the preparation of photocontrollable electrodes.
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Self-arrangement among charge-stabilized gold nanoparticles on a dithiothreitol reactivated octanedithiol monolayer.
Gold surfaces and structures modified with octanedithiol were reacted with dithiothreitol prior to immersion in buffered solutions of charge stabilized gold nanoparticles. The procedure gives a dithiol layer with adequate properties for a homogeneous octanedithiol monolayer and uniform and reproducible gold nanoparticle binding. The distance between the adsorbing particles is controlled by the particle electrostatic interactions and can be carefully tuned by variation of ionic strength. To some extent, long-range ordering occurs among the adsorbed particles. This behavior is facilitated by the particles' small size compared to the Debye screening but also by the homogeneity of the surface modification. The simple character of the system makes it attractive for fabrication of controlled nanoparticle arrays where further chemical and biological modifications are required.
18,928,323
Improving psychostimulant adherence in children with ADHD.
Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder of childhood, characterized by excessive inattention, hyperactivity and impulsivity. Effective medication exists for the condition, yet suboptimal long-term effects persist for children with ADHD. Poor adherence is a common issue for individuals with chronic conditions, including children and those with psychiatric conditions, and ADHD is no exception. This review examines the available evidence regarding patterns of long-term use of stimulant medication and the predictors of medication discontinuation among children with ADHD, and suggests future clinical and research directions for improving adherence in children with ADHD.
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Peripheral intracranial aneurysms: management challenges in 60 consecutive cases.
The authors report the management and outcomes of 55 patients with 60 intracranial aneurysms arising distal to the major branch points of the circle of Willis and vertebrobasilar system. Between July 1997 and December 2006, the authors' neurovascular service treated 2021 intracranial aneurysms in 1850 patients. The database was reviewed retrospectively to identify peripherally located intracranial aneurysms. Aneurysms that were mycotic and aneurysms that were associated with either an arteriovenous malformation or an atrial myxoma were excluded from review. The authors encountered 60 peripheral intracranial aneurysms in 55 patients. There were 42 small, 7 large, and 11 giant lesions. Forty-one (68%) were unruptured, and 19 (32%) had bled. Fifty-three aneurysms were treated surgically by using direct clip reconstruction in 26, trapping or proximal occlusion with distal revascularization in 21, excision with end-to-end anastomosis in 3, and circumferential wrap/clip reconstruction in 3. Coils were used to treat 6 aneurysms, and 1 was treated by endovascular parent artery occlusion. Overall, 49 patients had good outcomes, 4 were left with new neurological deficits, and 2 died. Peripherally situated intracranial aneurysms are rare lesions that present unique management challenges. Despite the fact that in the authors' experience these lesions were rarely treatable with simple clipping of the aneurysm neck or endovascular coil occlusion, preservation of the parent artery was possible in most cases, and the majority of patients had a good outcome.
18,928,355
NOD-like receptors: role in innate immunity and inflammatory disease.
The NOD-like receptors (NLRs) are a specialized group of intracellular receptors that represent a key component of the host innate immune system. Since the discovery of the first NLR almost 10 years ago, the study of this special class of microbial sensors has burgeoned; consequently, a better understanding of the mechanism by which these receptors recognize microbes and other danger signals and of how they activate inflammatory signaling pathways has emerged. Moreover, in addition to their primary role in host defense against invading pathogens, their ability to regulate nuclear factor-kappa B (NF-kappaB) signaling, interleukin-1-beta (IL-1beta) production, and cell death indicates that they are crucial to the pathogenesis of a variety of inflammatory human diseases.
18,928,408
Psychotropic medication utilization at a group-home residential facility for children and adolescents.
The purpose of this study was to examine psychotropic medication utilization over the course of treatment for children and adolescents admitted to a large residential group-home facility for youth with emotional and behavioral disorders. Retrospective analyses of psychotropic medication utilization at admission, during treatment, and at departure were examined for 1,010 children and adolescents consecutively admitted to the facility during 2001-2004. The relationship between psychotropic medication utilization and demographic variables, psychiatric diagnoses, objective measures of behavioral and emotional problems, in-program behavior, and ratings of program success were examined. The overall utilization rate was 49%, and there was a significant reduction in utilization from admission (40%) to departure (26%). Reductions were evident across all medication classes (e.g., stimulants, antipsychotics, etc.). At admission, medication utilization was related to several psychosocial variables, higher scores on measures of behavioral and emotional problems, and psychiatric diagnoses (attention-deficit/hyperactivity disorder (ADHD) and mood disorders). A small percentage (16%) of youth was prescribed novel medication during stay. Being placed on medication during treatment was related to internalizing problems on the Child Behavior Checklist (CBCL) at admission, psychiatric diagnoses, higher rates of in-program behavior problems, and poorer outcomes at departure. Youth departing on medication were more likely to be male, younger, and rated as doing more poorly in the program. They also were more likely to be placed in more restrictive settings at follow-up. There was a high rate of psychotropic medication utilization among this population, though utilization rates dropped significantly over the course of treatment.
18,928,416
Melatonin prevents age-related mitochondrial dysfunction in rat brain via cardiolipin protection.
Reactive oxygen species (ROS) are considered a key factor in brain aging process. Complex I of the mitochondrial respiration chain is an important site of ROS production and hence a potential contributor to brain functional changes with aging. Appropriate antioxidant strategies could be particularly useful to limit this ROS production and associated mitochondrial dysfunction. Melatonin has been shown to possess antioxidant properties and to reduce oxidant events in brain aging. The mechanism underlying this protective effect of melatonin is not well established. In the present study, we examined the effects of long-term treatment of aged rats with melatonin on various parameters related to mitochondrial bioenergetics in brain tissue. After isolation of mitochondria from control, aged, and melatonin-treated young and aged rats, various bioenergetic parameters were evaluated such as complex I activity, rates of state 3 respiration, mitochondrial hydrogen peroxide (H2O2) production, and membrane potential. The mitochondrial content of normal and oxidized cardiolipin was also evaluated. We found that all these mitochondrial parameters were significantly altered with aging, and that melatonin treatment completely prevented these age-related alterations. These effects appear to be due, at least in part, to melatonin's ability to preserve the content and structural integrity of cardiolipin molecules, which play a pivotal role in mitochondrial bioenergetics. The melatonin's ability to prevent complex I dysfunction and cardiolipin peroxidation was also demonstrated by in vitro experiments on brain mitochondria treated with tert-butyl hydroperoxide. In summary, this study documents a decline of mitochondrial bioenergetic functions in brain with aging and the beneficial effect of melatonin.
18,928,424
Hepatosplenic T-cell lymphoma following infliximab therapy for Crohn's disease.
Tumour necrosis factor inhibitors have revolutionised the management of Crohn's disease, but reports of a possible association between concomitant infliximab and immunomodulator therapy and hepatosplenic T-cell lymphoma (a rare form of aggressive non-Hodgkin's lymphoma) have emerged. We describe the first case in Australia of hepatosplenic T-cell lymphoma in a patient who had been treated with infliximab and immunomodulators for Crohn's disease.
18,928,444
Hyperinsulinism and hyperammonaemia syndrome due to a novel missense mutation in the allosteric domain of the glutamate dehydrogenase 1 gene.
Congenital hyperinsulinism is one of the causes of persistent hypoglycaemia in neonates and infants. We describe a one-month-old boy with a rare form of congenital hyperinsulinism characterised by hypoglycaemia and hyperammonaemia.
18,928,469
Combined magnetic resonance coronary artery imaging, myocardial perfusion and late gadolinium enhancement in patients with suspected coronary artery disease.
Cardiovascular magnetic resonance (CMR) imaging offers methods for the detection of ischemia and myocardial infarction as well as visualization of the coronary arteries (MRCA). However, a direct comparison of adenosine perfusion (PERF), late gadolinium enhancement (LGE) and MRCA or the results of their combination has not been performed. Aim of the study was to evaluate the feasibility/diagnostic performance of rest/stress perfusion, late gadolinium enhancement and MRCA and their combination in patients with suspected coronary artery disease (CAD) in comparison to invasive angiography. Fifty-four patients (60 +/- 10 years, 35 men, CAD 48%) underwent CMR including MRCA (steady state free precession, navigator whole heart approach, spatial resolution 0.7 x 0.7 x .0.9 mm, trigger delay and temporal resolution adjusted individually), stress PERF (adenosine 140 mug/min/kg), rest PERF (SSFP, 3 short axis, 1 saturation prepulse per slice) and LGE (3D inversion recovery technique) using Gd-BOPTA. Images were analyzed visually. Stenosis >50% in invasive angiography was considered significant. Mean study time was 68 +/- 11 minutes. Sensitivity for PERF, LGE, MRCA and the combination of PERF/LGE and PERF/LGE/MRCA was 87%, 50%, 91%, 88% and 92%, respectively and specificity 88%, 96%, 46%, 88% and 56%, respectively. If image quality of MRCA was excellent (n = 18) the combination of MRCA/PERF/LGE yield a sensitivity of 86% and specificity of 91%. However, no test or combination improved diagnostic performance significantly compared to PERF alone. In patients with CAD, the combination of stress PERF, LGE and MRCA is feasible. When compared to invasive angiography, adenosine stress perfusion outperforms CMR coronary angiography in direct comparison and yields the best results with non-significant improvement in combination with LGE and significant deterioration in combination with MRCA. MRCA may be of additional value only in a minority of patients with excellent image quality.
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SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys.
Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide. We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123-270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis. These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.
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Homoeologous gene silencing in tissue cultured wheat callus.
In contrast to diploids, most polyploid plant species, which include the hexaploid bread wheat, possess an additional layer of epigenetic complexity. Several studies have demonstrated that polyploids are affected by homoeologous gene silencing, a process in which sub-genomic genomic copies are selectively transcriptionally inactivated. This form of silencing can be tissue specific and may be linked to developmental or stress responses. Evidence was sought as to whether the frequency of homoeologous silencing in in vitro cultured wheat callus differ from that in differentiated organs, given that disorganized cells are associated with a globally lower level of DNA methylation. Using a reverse transcription PCR (RT-PCR) single strand conformation polymorphism (SSCP) platform to detect the pattern of expression of 20 homoeologous sets of single-copy genes known to be affected by this form of silencing in the root and/or leaf, we observed no silencing in any of the wheat callus tissue tested. Our results suggest that much of the homoeologous silencing observed in differentiated tissues is probably under epigenetic control, rather than being linked to genomic instability arising from allopolyploidization. This study reinforces the notion of plasticity in the wheat epi-genome.
18,928,533
School based screening for tuberculosis infection in Norway: comparison of positive tuberculin skin test with interferon-gamma release assay.
In Norway, screening for tuberculosis infection by tuberculin skin test (TST) has been offered for several decades to all children in 9th grade of school, prior to BCG-vaccination. The incidence of tuberculosis in Norway is low and infection with M. tuberculosis is considered rare. QuantiFERONTB Gold (QFT) is a new and specific blood test for tuberculosis infection. So far, there have been few reports of QFT used in screening of predominantly unexposed, healthy, TST-positive children, including first and second generation immigrants. In order to evaluate the current TST screening and BCG-vaccination programme we aimed to (1) measure the prevalence of QFT positivity among TST positive children identified in the school based screening, and (2) measure the association between demographic and clinical risk factors for tuberculosis infection and QFT positivity. This cross-sectional multi-centre study was conducted during the school year 2005-6 and the TST positive children were recruited from seven public hospitals covering rural and urban areas in Norway. Participation included a QFT test and a questionnaire regarding demographic and clinical risk factors for latent infection. All positive QFT results were confirmed by re-analysis of the same plasma sample. If the confirmatory test was negative the result was reported as non-conclusive and the participant was offered a new test. Among 511 TST positive children only 9% (44) had a confirmed positive QFT result. QFT positivity was associated with larger TST induration, origin outside Western countries and known exposure to tuberculosis. Most children (79%) had TST reactions in the range of 6-14 mm; 5% of these were QFT positive. Discrepant results between the tests were common even for TST reactions above 15 mm, as only 22 % had a positive QFT. The results support the assumption that factors other than tuberculosis infection are widely contributing to positive TST results in this group and indicate the improved specificity of QFT for latent tuberculosis. Our study suggests a very low prevalence of latent tuberculosis infection among 9th grade school children in Norway. The result will inform the discussion in Norway of the usefulness of the current TST screening and BCG-policy.
18,928,541
A candidate molecular signature associated with tamoxifen failure in primary breast cancer.
Few markers are available that can predict response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancers. Identification of such markers would be clinically useful. We attempted to identify molecular markers associated with tamoxifen failure in breast cancer. Eighteen initially ER-positive patients treated with tamoxifen requiring salvage surgery (tamoxifen failure [TF] patients) were compared with 17 patients who were disease free 5 years after surgery plus tamoxifen adjuvant therapy (control patients). cDNA microarray, real-time quantitative PCR, and immunohistochemistry on tissue microarrays were used to generate and confirm a gene signature associated with tamoxifen failure. An independent series of 33 breast tumor samples from patients who relapsed (n = 14) or did not relapse (n = 19) under tamoxifen treatment from a different geographic location was subsequently used to explore the gene expression signature identified. Using a screening set of 18 tumor samples (from eight control patients and 10 TF patients), a 47-gene signature discriminating between TF and control samples was identified using cDNA arrays. In addition to ESR1/ERalpha, the top-ranked genes selected by statistical cross-analyses were MET, FOS, SNCG, IGFBP4, and BCL2, which were subsequently validated in a larger set of tumor samples (from 17 control patients and 18 TF patients). Confirmation at the protein level by tissue microarray immunohistochemistry was observed for ER-alpha, gamma-synuclein, and insulin-like growth factor binding protein 4 proteins in the 35 original samples. In an independent series of breast tumor samples (19 nonrelapsing and 14 relapsing), reduced expression of ESR1/ERalpha, IGFBP4, SNCG, BCL2, and FOS was observed in the relapsing group and was associated with a shorter overall survival. Low mRNA expression levels of ESR1/ERalpha, BCL2, and FOS were also associated with a shorter relapse-free survival (RFS). Using a Cox multivariate regression analysis, we identified BCL2 and FOS as independent prognostic markers associated with RFS. Finally, the BCL2/FOS signature was demonstrated to have more accurate prognostic value for RFS than ESR1/ERalpha alone (likelihood ratio test). We identified molecular markers including a BCL2/FOS signature associated with tamoxifen failure; these markers may have clinical potential in the management of ER-positive breast cancer.
18,928,543
Insulin sensitivity is normalized in the third generation (F3) offspring of developmentally programmed insulin resistant (F2) rats fed an energy-restricted diet.
The offspring and grandoffspring of female rats fed low protein diets during pregnancy and lactation, but fed nutritionally adequate diets thereafter, have been shown to exhibit altered insulin sensitivity in adulthood. The current study investigates the insulin sensitivity of the offspring and grandoffspring of female rats fed low protein diets during pregnancy, and then maintained on energy-restricted diets post weaning over three generations. Female Sprague Dawley rats (F0) were mated with control males and protein malnourished during pregnancy/lactation. F1 offspring were then weaned to adequate but energy-restricted diets into adulthood. F1 dams were fed energy-restricted diets throughout pregnancy/lactation. F2 offspring were also fed energy-restricted diets post weaning. F2 pregnant dams were maintained as described above. Their F3 offspring were split into two groups; one was maintained on the energy-restricted diet, the other was maintained on an adequate diet consumed ad libitum post weaning. F2 animals fed energy-restricted diets were insulin resistant (p < 0.05), while the insulin sensitivity of their F3 offspring equaled and surpassed that of controls on both the energy-restricted and adequate ad libitum postweaning diets (p < 0.05). Maternal energy-restriction did not consistently program reduced insulin sensitivity in offspring over three consecutive generations. The reasons for this remain unclear. It is possible that the intergenerational transmission of developmentally programmed insulin resistance is determined in part by the relative insulin sensitivity of the mother during pregnancy/lactation.
18,928,547
A qualitative exploration of prescription opioid injection among street-based drug users in Toronto: behaviours, preferences and drug availability.
There is evidence of a high prevalence of prescription opioid (PO) and crack use among street drug users in Toronto. The purpose of this qualitative study was to describe drug use behaviours and preferences as well as the social and environmental context surrounding the use of these drugs among young and old street-based drug injection drug users (IDUs). In-depth interviews were conducted with 25 PO injectors. Topics covered included drug use history, types of drugs used, how drugs were purchased and transitions to PO use. Interviews were taped and transcribed. Content analysis was conducted to identify themes. Five prominent themes emerged from the interviews: 1) Combination of crack and prescription opioids, 2) First injection experience and transition to prescription opioids, 3) Drug preferences and availability, 4) Housing and income and 5) Obtaining drugs. There was consensus that OxyContin and crack were the most commonly available drugs on the streets of Toronto. Drug use preferences and behaviours were influenced by the availability of drugs, the desired effect, ease of administration and expectations around the purity of the drugs. Distinct experiences were observed among younger users as compared to older users. In particular, the initiation of injection drug use and experimentation with POs among younger users was influenced by their experiences on the street, their peers and general curiosity. Given the current profile of street-based drug market in Toronto and the emergence of crack and POs as two predominant illicit drug groups, understanding drug use patterns and socio-economic factors among younger and older users in this population has important implications for preventive and therapeutic interventions.
18,928,556
Bladder incarceration following anterior external fixation of a traumatic pubic symphysis diastasis treated with immediate open reduction and internal fixation.
Anterior pelvic ring disruptions are often associated with injuries to the genitourinary structures with the potential for considerable resultant morbidity. Herniation of the bladder into the symphyseal region after injury with subsequent entrapment upon reduction of the symphyseal diastasis has seldom been reported in the literature. We report such a case involving bladder herniation and subsequent entrapment after attempted closed reduction with anterior pelvic external fixation immediately treated with open reduction and internal fixation along with a review of the literature.
18,928,569
[Immunoregulatory effect of mesenchymal stem cells on active T lymphocytes].
This study was purposed to explore the immunoregulatory effects of human bone marrow mesenchymal stem cells (MSCs) on active T lymphocytes in vitro and the new strategy to prevent graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mononuclear cells from human peripheral blood cells were isolated and cultured in the presence of phytohemagglutinin (PHA) (final concentration was 10 microg/ml) for different times. The ability of T lymphocyte proliferation and activation was measured by (3)H-Thyramine incorporation. The expressions of CD3(+)CD4(+), CD3(+)CD8(+), CD4(+)CD25(+) and CD4(+)CD152(+) on T cells were detected by FCM after coculture for 72 hours. Experiment was divided into 4 groups: A group as control (no added MSCs), B group (actived T cells + 2 x 10(4) MSCs), C group (actived T cells + 4 x 10(4) MSCs), D group (actived T cells + 8 x 10(4) MSCs). The results showed that the ability of T lymphocyte proliferation in the same PHA concentration increased with prolonging of time. ability of T lymphocyte proliferation was strongest when culturing for 48 hours (p < 0.01); the expressions of CD44, CD105, CD29 and FIK1 of MSCs were positive, expressions of CD33, CD34, CD45 and HLA-DR were negative. MSCs inhibited T lymphocyte proliferation and the inhibitory effect depended on the amount of MSCs. CD3(+)CD8(+), CD4(+)CD25(+) and CD4(+)CD152(+) T cells cocultured with MSCs increased obviously and CD3(+)CD4(+) expression significantly decreased, as compared with control group (p < 0.01). It is concluded that the MSCs inhibit T lymphocyte proliferation induced by mitogen (PHA), and perform their immunosuppressive function by up-regulation of CD3(+)CD8(+), CD4(+)CD25(+) and CD4(+)CD152(+) expressions and down-regulation of CD3(+)CD4(+) expression.
18,928,608
[Effect of PD-L1 blockade on function of dendritic cells derived from chronic myelocytic leukemia].
Programmed death-1 ligand-1(PD-L1) is a recently identified member of the B7 family molecules and is shown to mediate the inhibition of immune responses. This study was purposed to enhance the weak immunological function of dendritic cells (DCs) derived from the patients with chronic myelocytic leukemia (CML) by blockade of the expression of PD-L1. Bone marrow mononuclear cells (BMMNCs) of CML patients were induced into DCs in the presence of cytokine cocktail of rhGM-CSF, rhIL-4 and TNF-alpha. The phenotypes of DCs were detected by flow cytometry, mixed lymphocyte reaction was analyzed by MTT assay and IFN-gamma, IL-2 and IL-10 in the cell culture supernatant were detected by ELISA. The results showed that the expression of PD-L1 on CML-DCs was upregulated with the maturation of CML-DCs. PD-L1-blockaded DCs could enhance T lymphocyte proliferation, increase the secretion of IL-2 and IFN-gamma, and inhibit the production of IL-10. Taken together, PD-L1-blockaded DCs originated from CML cells had more potent immunostimulatory capability. It is concluded that PD-L1 blockaded can enhance the function of CML-DCs. This approach presents new possibilities for achieving anti-tumor immunity by DC-based vaccination.
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Biological activity of DC-CIK cells and its effect against leukemia cells in vitro.
This study was aimed to investigate the effect of dendritic cells (DC) on the proliferation capability, immunophenotype changes, level of secreted cytokines and activity against leukemia of cytokine-induced killer (CIK) cells in vitro. DCs and CIK cells were induced from peripheral blood mononuclear cells of healthy volunteers. They were co-cultured meanwhile CIK cells were cultured alone as controls. Increased number of cells were counted by trypan-blue staining; the killing activity was detected by MTT assay; immunophenotype changes were analyzed by flow cytometry; the IL-12 and INF-gamma levels of the cultured supernatants were detected by ELISA kits. The results showed that the proliferation capability of DC-CIK cells was significantly higher than that of CIK cells (p < 0.05). Under the same condition, the ratio of double positive cells such as CD3(+) CD8(+), CD3(+) CD56(+) in CIK cells was significantly enhanced by co-cultured with DC cells (p < 0.05). The levels of IL-12 and INF-gamma in cultured supernatants of DC-CIK cells increased noticeably on day 3 as compared with CIK cells cultured alone (p < 0.01, p < 0.05). Within the effector-target ratio range between 5:1 to 40:1, the activity of DC-CIK cells against leukemia cells were much higher than that of CIK cells (p < 0.05), and this effect showed a positive correlation with the effector-target ratio. It is concluded that the proliferation capability of DC-CIK cells, the level of their secreted cytokines and their activity against leukemia cells are significantly higher than those of CIK cells. This research may suggest an approach for clinical immunotherapy against leukemia with DC-CIK cells.
18,928,615
[Construction and selection of the most efficient siRNA interfering plasmid specific to mouse Qa-1 gene].
This study was purposed to construct three siRNA eukaryotic expression vector specific to mouse Qa-1 gene, to investigate its silencing effect on Qa-1 gene and to select the most efficient siRNA plasmid specific to mouse Qa-1 gene. Three siRNA peptides specific to mouse Qa-1 through siRNA Web design tools of Ambion company were chosed. Jingsai Company helped to complete the siRNA eukaryotic expression vector. The mouse NIH3T3 cells cultured in RPMI 1640 medium with 10% fetal bovine serum were divided into four groups: three groups of the cells were transfected with lipofectamine 2000 reagent and three different siRNA eukaryotic expression vectors, while one group cells were transfected with lipofectamine 2000 reagent alone as negative control. Cells were collected at 24, 48, 72 hours after transfection; the RNA level of Qa-1 was detected by RT-PCR, and the expression position was examined with flow cytometry analysis by using anti-Qa-1 monoclonal antibody. The results indicated that the constructed three siRNA eukaryotic expression vectors were found to be specific to mouse Qa-1 gene. The sequence analysis showed that the sequence was identical to what chosed from web tools. NIH3T3 cells in vitro were adhered in culture that cell shape appeared to change after transfection. RT-PCR and flow cytometry analysis by using anti-Qa-1 monoclonal antibody approved that both Qa-1 RNA and the expression of Qa-1 on cell surface decreased. The decreased levels in the three groups were different. At 24, 48 and 72 hours, the expression of Qa-1 on NIH3T3 cells decreased as in the following: H2-T231: 60.9%, 81.9%, 43.6%; H2-T232: 64.5%, 73.9%, 61.1%; H2-T233: 61.9%, 71.2%, 47.5%. H2-T232 was most efficient one in all three time points. It is concluded that all three siRNA eukaryotic expression vectors selected can successfully suppress the expression of the Qa-1, and from them H2-T232 is most efficient.
18,928,620
[GFP used as a reporter system for optimization of K562 cell transfection].
This study was aimed to obtain higher efficiency in gene transfection into K562 cells and to study the role of green fluorescence protein (GFP) as a reporter system. Transfection efficiencies with different methods including electroporation and lipofectamine 2000 transfection, were observed and calculated under fluorescent microscopy by using GFP as a reporter system. The results showed that the transfection efficiency with electroporation (10%) was higher than that with lipofectamine 2000 (1%). In conclusion, the electroporation is a more ideal method for introduction of foreign gene into K562 cells. GFP can be used as a reporter system for optimizing transfection of K562 cells.
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[Effect of prefreezing parameters on human platelet cryopreservation].
This study was aimed to investigate the effect of prefreezing parameters such as freezing rate, annealing, rate, annealing temperature, holding time in annealing before lyophilization on lyophilized platelets by orthogonal tests. The recovery rate, the morphological and ultrastructural changes, the activation and aggregation of lyophilized platelet after rehydratation were detected by cytometer, scan electron microscopy, flow cytometry and aggregation reaction on thrombin, respectively, and complex evaluation was carried out. The results showed that the recovery rate of lyophilized platelets was 91% - 53.5% at different conditions of lyophilization, the size and shape of ice crystals in lyophilized platelets of different test groups were not similar, the expression and distribution of platelet activation markers (PAC-1 and CD62p) after rehydration were relatively similar to fresh platelets, expression rate of PAC-1 was lower (0.03% - 0.22%), meanwhile there were differences of CD62p expression levels between different groups. The optimal theoretic composition of prefreezing conditions obtained on basis of platelet recovery rate was A(2)B(1)C(1)D(3), i.e, first, suspensions of platelets on the program control cooling apparatus were lyophilized with a rate of 20 degrees C/min and maintained at -40 degrees C for 2 hours, then the annealing was conducted at -30 degrees C for 0.5 hours with a heating rate of 1.5 degrees C/min; finally, the freeze-drying program was carried out to the end. It is concluded that the freezing rate, annealing rate, annealing temperature and holding time of annealing all impact on the recovery of lyophilized platelets. The preservation qualities of lyophilized platelets were affected by the various combinations of prefreezing parameters.
18,928,628
[Curative effect of rhIL-11 on 26 patients with chromic idiopathic thrombocytopenic purpura].
Traditional treatment of chronic idiopathic thrombocytopenic purpura (CITP) is usually adopted as hormonal therapy. If necessary, it also can be given immunosuppressive therapy. In order to investigate the curative effect of rhIL-11 on patients with ITP, 26 patients were divided into control group and rhIL-11 group, each group with 13 patients. Control group was given traditional hormonal therapy and immunosuppressive therapy, while rhIL-11 group was given rhIL-11 on base of traditional therapy. rhIL-11 25 microg/(kg.d) was injected s.c. for 28 days. The results showed that 23 out of 26 patients obtained obviously curative effect in platelet count, especially in rhIL-11 group, but another 3 patients had no response on therapy. The platelet counts of control and rhIL-11 groups increased from 26.15 x 10(9)/L and 27.84 x 10(9)/L before treatment to 66.62 x 10(9)/L and 105.62 x 10(9)/L after treatment. The platelet count of rhIL-11 group after treatment was remarkably higher than that of the control group (p < 0.05). Platelet count of 8 patients in rhIL-11 group recovered to normal. It is concluded that rhIL-11 combined with traditional hormone-immuno-suppressive therapy is effective to CITP.
18,928,632
[Clinical significance of Helicobacter pylori in pathogenesis of idiopathic thrombocytopenic purpura].
This study was purposed to investigate the infection incidence of Helicobacter pylori (HP) in patients with idiopathic thrombocytopenic purpura (ITP) and curative efficacy of glucocorticoids combined with anti-helicobacter. 100 ITP patients with positive HP were divided randomly into 3 groups: glucocorticoid group (treatment with glucocorticoids, n = 35), anti-HP treatment group (HP eradication, n = 30) and combined treatment group (glucocorticoid combined with HP eradication, n = 35). 100 healthy individuals were selected as control. The results showed that HP infection rate in ITP group was 70%, while HP infection rate in control group (persons received physical examination) was 56%, there was significant difference between two groups (p < 0.05). The HP of 31 cases in combined treatment group was eradicated that the platelet count in 23 out of 31 cases recovered to normal, and in 8 cases was higher than that before treatment, which mean count was (165 +/- 225) x 10(9)/L, this value had statistical significance as compared with that before treatment (p < 0.01). Total efficiency in this group reached to 89%, and relapse rate within 1 year was 8%. The HP infection of 2 cases in glucocorticoid group had been turned to negative naturally, and platelet count recovered to normal, while HP infection in remained 33 cases was still positive. The platelet count in 23 out of 33 cases of that group was not back to normal, but back to normal in 10 cases. The platelet mean count in that group was (78 +/- 26) x 10(9)/L with total efficiency rate of 68% and relapse rate within 1 year was 37%. In the anti-HP treatment group, HP infection in 25 cases was eradicated and platelet count in 9 out of 25 cases recovered to normal, that platelet count in 9 cases was higher than that before treatment, platelet mean count was (135 +/- 174) x 10(9)/L), there was significant difference (p < 0.01), as compared with value before treatment. Total efficiency rate in this group reached to 60%, and relapse rate within 1 year was 33%. It is concluded that the patients with ITP have higher HP infection incidence, and the eradication of HP is effective therapy for the ITP patients with HP infection, which can be used as initial treatment.
18,928,633
Morphological study of fibroblasts treated with cytochalasin D and colchicine using a confocal laser scanning microscopy.
The role of actin filaments and microtubules in 3D cell morphology was investigated using confocal laser scanning microscopy and image analysis based on a region-growing method. Fibroblasts were treated with cytochalasin D or colchicine to disrupt the actin filaments or microtubules, respectively, and the structure and distribution of these cytoskeletal filaments were observed using a confocal laser scanning microscope. From the 3D reconstructed fluorescence images of the cytoskeleton, morphological parameters such as volume, adhesion area, height, and volume ratio of individual cells were determined. The volume ratio was defined as the ratio of the partial volume for every 10% of the height to the total cell volume. The cell volume decreased slightly after the disruption of actin filaments and microtubules, but the change was not significant. The cell adhesion area was significantly decreased after the disruption of actin filaments and microtubules, and was significantly smaller in actin filament-disrupted cells than in microtubule-disrupted cells. Cell height increased significantly after actin filament disruption, whereas it remained almost unchanged after microtubule disruption. Analysis of the volume ratio revealed that the cell shape changed from a cone to a hemisphere after disruption of actin filaments and slightly shifted toward a hemisphere-like shape after microtubule disruption. These results suggest that actin filaments are the major component responsible for the maintenance of global cell shape and that the contribution of microtubules to global cell morphology is much less than that of actin filaments.
18,928,641
Notch signaling in pediatric malignancies.
Notch signaling plays crucial roles in many developmental pathways, with Notch mutations linked to several developmental disorders. Because many pediatric malignancies arise from dysregulated development, roles for Notch signaling in these cancers are to be expected. Evidence to support this is now emerging as the Notch pathway is being explored in more pediatric cancers. Not surprisingly, Notch appears to play diverse roles in different malignancies, effecting differentiation, metastasis, cancer "stem cells," and angiogenesis. As examples, although activating mutations of Notch1 are found in the majority of T-cell acute lymphoblastic leukemia (ALL) cases, Notch/HES1 signaling appears to play a tumor suppressor role in precursor B-cell ALL; although Notch/HES1 signaling appears to contribute to osteosarcoma metastasis, Notch signaling also promotes medulloblastoma "stem cell" survival and contributes to angiogenesis in neuroblastoma. Further understanding of the roles of Notch signaling in specific pediatric cancers will provide a rationale for Notch-based therapeutic strategies.
18,928,660
Pediatric developmental therapies: interesting new drugs now in early-stage clinical trials.
The current high cure rates for children diagnosed with cancer can be attributed in part to emphasis on large cooperative group clinical trials. The significant improvement in pediatric cancer survival over the past few decades is the result of optimized chemotherapy drug dosing, timing, and intensity; however, further alterations in traditional chemotherapy agents are unlikely to produce substantially better outcomes. Furthermore, there remains a subset of patients who have a very poor prognosis due to tumor type or stage at presentation, or who have a dismal prognosis with relapse or recurrence. As such, innovative approaches to therapy and new drugs are clearly needed for introduction into the current pediatric oncology arsenal. A variety of biologically targeted therapies that have shown promise in preclinical studies and early-phase adult clinical trials are now being explored in pediatric clinical trials. These novel agents hold the promise for continuing to drive forward improvements in patient survival, with potentially less toxicity than exists with traditional chemotherapy drugs.
18,928,662
Human papillomavirus testing for primary cervical cancer screening.
With our understanding of human papillomavirus (HPV) and cervical cancer, the availability of HPV testing, and the known limitations of cervical cytology, it is time to reassess cervical cancer screening technologies. This article reviews recent randomized trials comparing primary HPV testing with cervical cytology in screening for cervical cancer, and also analyzes the impact of the HPV vaccine on screening cytology.
18,928,670
[Ontogenic development of the incudostapedial joint].
To study the development of the incudostapedial joint in human embryos and foetuses. 46 temporal bones with specimens between 9 mm and newborns were studied. The preparations were sliced serially and dyed using the Martins trichrome technique. The incudostapedial joint takes on the characteristics of a spheroidal joint at 16 weeks of development. The cartilage covering the articular surfaces is formed by different strata that develop in succession: the superficial stratum at 19 weeks, the transitional between 20 and 23 weeks, and the radial from 24 weeks on. The subchondral bone develops after 29 weeks by the mechanisms of apposition and extension of the periosteal and endosteal bones, but it is not until week 34 that it completely covers the articular surfaces, following constitution of the bone fascicles transmitting the lines of force. The articular capsule is formed from the inter-zone, the surface zone develops the capsular ligament, and the internal surface develops the synovial membrane. At the time of birth, the incudostapedial joint is completely developed.
18,928,674
[Congenital disorder of glycosylation type 1b. Experience with mannose treatment].
Congenital disorders of glycosylation (CDG) are recessively inherited multisystemic disorders resulting from several genetic defects affecting the assembly, transfer or processing of oligosaccharides onto proteins and other glycoconjugates. CDG type Ib is due to a deficiency of phosphomannose isomerase (PMI) encoded by the MPI gene. PMI catalyzes the interconversion of fructose-6-P and mannose-6-P. The clinical phenotype is characterized by gastro-intestinal and hepatic symptoms. In contrast to most CDG patients, there is no neurological affectation. It's a mannose treatable disorder. We report the first recognised case of CDG Ib in Spain. He presented at 6 months with hypoglycaemia, failure to thrive and hypertransaminasaemia. He subsequently developed an enteropathy with subtotal villous atrophy on biopsy. The %CDT was very high and he presented with a type 1 pattern in transferrin isoelectric focusing. PMI activity in fibroblasts was very deficient. Mutations in MPI gene at R219Q and R56fs were found. Clinical and biochemical parameters normalised after treatment with mannose 1 g/kg/day in 5 doses. CDG Ib should be considered in patients with hypoglycaemia, liver disease, enteropathy and hypercoagulability, in the absence of other common causes, and particularly if some of them are combined.
18,928,705
[Hemoglobin Stanleyville II [alpha78(EF7)Asn --> Lys]. First case described in Spain].
Structural hemoglobinopathies are the result of mutations in the genes of globin, which determine a qualitative alteration in the expression of these genes. Most alterations do not originate any significant change, and correspond to silent or asymptomatic forms. This study proves a new case of hemoglobin (Hb) Stanleyville II. The propositus was a 72 years old Caucasian woman, from the Canary Islands. Her hematological data were: Hb 14.3 g/dl; hematocrit 44.4%; mean corpuscular volume 85.8 fl; mean corpuscular hemoglobin 27.7 pg; red cell distribution width 15.1%; reticulocytes 1.2%; HbA2 3.1% and HbF 1.6%. Electrophoretic studies in cellulose acetate electrophoresis at alkaline pH = 8.6 and isoelectrofocusing showed an anomalous Hb similar to HbS. The anomalous Hb did not appear in agar citrate electrophoresis (pH 6.0). The analysis by reverse phase high performance liquid chromatography for globin chains showed an X anomalous after A. Molecular analysis by sequentiation of the polymerase chain reaction products genes 1 and 2 showed the mutation AAC --> AAA at CD78 of second gene 2 in heterozygote state, which leads the change of asparagine to lysine. The substitution of an amino acid with neutral charge like asparagine for another one with positive charge like lysine in the segment EF, which corresponds to the external surface of the tertiary structure of the chain of globin, determines the change of charge in the chain. This allows an easy differentiation by electrophoretic and chromatographic methods. Nevertheless, owing to its position in the chain, which is not critique for the stability, solubility and affinity for the oxygen allows for silent or asymptomatic forms. The Hb Stanleyville II had been described before in black families of the Congo, Uganda, USA, Alsace and Brazil. This case represents the first case described in Spain.
18,928,738
[Obesity in the history of surgery].
Obesity is a problem that is reaching epidemic proportions throughout the world and bariatric surgery is now a rapidly growing technique. However existence of obesity in humans has been recognized for thousands of years, as statues dating from the Stone Age period appear to provide the earliest depictions. Hippocrates (466-355 b.C.) and Galen (131-201 a.C.) had a clear understanding of the condition, its consequences and medical treatment. On the other hand bariatric surgery was a xx century treatment, but at the end of the xix century it was known that the massive loss of small bowel or gastric resection after ulcer surgery resulted in persistent weight loss. Malabsorption and gastric restriction in isolation, or more commonly in combination, remain the main options to surgical control of weight. Unfortunately surgery as a non etiological treatment is an imperfect model to treat an incurable disease: morbid obesity. Prevention and better knowledge of disease would allow a tailored medical or surgical approach.
18,928,768
Drug-eluting stents in the real world: how intravascular ultrasound can improve clinical outcome.
Although the benefits of drug-eluting stents for the treatment of native coronary lesions in patients undergoing percutaneous coronary interventions have been demonstrated in multiple clinical trials, there remains concern about the risk of late stent thrombosis. The MATRIX registry, a prospective study designed to reflect clinical conditions, has enrolled a varied population of complex patients who have received the sirolimus-eluting stent (SES) and long-term dual antiplatelet therapy. Contributing to the low rate of stent thrombosis and other complications after SES deployment in this study is the routine use of intravascular ultrasound (IVUS) imaging before and after implantation at a high rate (38%). Important technical considerations for the IVUS operator include stent expansion, residual edge stenosis, and malapposition. Ensuring adequate stent dimensions and wall contact can contribute to successful outcomes in patients receiving SES.
18,928,789
Drug-eluting stents and antiplatelet resistance.
Resistance to the antiplatelet effects of both aspirin and clopidogrel is common and is associated with poorer clinical outcomes in patients receiving antiplatelet therapy. Available data indicate that hyporesponsiveness to clopidogrel is overcome in some patients by increasing the loading dose from 300 mg to 600 mg, with the higher loading dose being associated with reduced risk for adverse cardiovascular outcomes. Recent studies in patients undergoing coronary stent implantation indicate that antiplatelet resistance is associated with increased risk of stent thrombosis. A study in 804 patients receiving drug-eluting stents showed that nonresponse (defined as >70% aggregation at 10 micromol/L adenosine diphosphate) after a clopidogrel 600-mg loading dose was associated with a significantly increased risk of stent thrombosis (8.6% vs 2.3% for nonresponders vs responders, respectively) and cardiovascular death at 6 months. Another study in 380 patients showed that high posttreatment platelet reactivity (top tertile of values) on a rapid assay was associated with significantly greater out-of-hospital 6-month rates of stent thrombosis (4.0% vs 0.4% for high posttreatment reactivity group vs low posttreatment reactivity group, respectively), cardiovascular death, and nonfatal myocardial infarction. Further studies are needed to provide standardized definitions of antiplatelet resistance to better correlate resistance with clinical outcomes in patients receiving stents and to identify treatment alternatives in patients with resistance.
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[Osteoporosis and the orthopaedic surgeon in 2007].
Despite advances in the prevention and treatment of fragility fractures, their prevalence continues to grow. The identification and treatment of osteoporosis in these high-risk patients are widely reported to be inadequate. The results of the 2002 and 2006 "Orthopaedic Surgeon Survey" under the auspice of BJD and IOF have shown a better involvement of the orthopaedic surgeon in osteoporosis management during his routine clinical practice. The orthopaedic surgeons knew that fragility fractures in patient over 50 years old require investigation for osteoporosis. Although some surgeons agreed to initiate investigation and inform patient about new osteoporosis fracture risk, the majority did not institute medical treatment and thought that the patient primary care provider or rheumatologist should be responsible for medical care. This round table highlights the current aspect of management of fragility fractures and focuses on diagnosis imaging techniques, pharmacological treatment as well as recent advances in implant design and surgical techniques.
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Preventing cancer.
Advancements in management protocols and chemotherapeutics have improved outcomes for patients diagnosed with cancer. Cancer, however, continues to claim many lives annually in the United States and around the world. There is a large body of evidence that is strong and consistent that through modification of diet and lifestyle habits, cancer can be a preventable disease. This article discusses these changes and highlights the evidence for and against implementing them.
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Disease prevention and wellness in the twenty-first century.
Primary care physicians should continue their efforts in disease prevention and also should expand their scope of service to support patients' interests in wellness and health optimization. Taking on this role will require additional time and continuing education, but by knowledgeably helping patients to maximize their health, physicians will provide a needed service, contribute to the health of their patients, and reap the rewards of a stronger doctor-patient bond.
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Comparison of the anesthetic efficacy of the conventional inferior alveolar, Gow-Gates, and Vazirani-Akinosi techniques.
The purpose of this prospective, randomized study was to compare the degree of pulpal anesthesia obtained with the conventional inferior alveolar, the Gow-Gates, and the Vazirani-Akinosi techniques in vital, asymptomatic teeth. With a crossover design, 40 subjects received all 3 techniques in a random manner by using 3.6 mL of 2% lidocaine with 1:100,000 epinephrine at 3 separate appointments. An electric pulp tester was used to test for anesthesia in 3-minute cycles for 60 minutes of the first molars, first premolars, and lateral incisors. Anesthesia was considered successful when 2 consecutive 80 readings were obtained within 15 minutes, and the 80 reading was continuously sustained through the 60th minute. The ranges of successful anesthesia were as follows: inferior alveolar technique, 25%-62%; Gow-Gates technique, 16%-44%; and for the Vazirani-Akinosi technique, 13%-50%. There was no significant difference (P > .05) in success among the 3 techniques. However, the Gow-Gates and Vazirani-Akinosi techniques resulted in a statistically slower onset of pulpal anesthesia than the inferior alveolar nerve block. We concluded that in vital, asymptomatic teeth and for the subjects who achieved lip numbness, the conventional inferior alveolar nerve block is similar to the Gow-Gates and Vazirani-Akinosi techniques regarding anesthetic success but has a faster onset of pulpal anesthesia.
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The onset and course of binge eating in 8- to 13-year-old healthy weight, overweight and obese children.
This study aimed to (1) determine the prevalence of binge eating and overeating in 8- to 13-year-old children; (2) identify factors that cross-sectionally predict binge eating and overeating; and (3) identify factors that prospectively predict onset of binge eating and overeating. Participants were 259 boys and girls who were assessed at baseline and one-year follow-up, using a range of semi-structured interviews that included the Child Eating Disorder Examination. At baseline, 9% of children reported binge eating and 6% reported overeating. Obese children were most at risk for these behaviours. Dietary restraint and the tendency to use food to regulate emotions were significant in predicting binge eating onset prospectively, and eating concern was significant in predicting binge eating cross-sectionally. Results provide support for current cognitive-behavioural models of binge eating, and have implications for guiding binge eating prevention and intervention efforts with children.
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Race is a predictor of in-hospital mortality after cholecystectomy, especially in those with portal hypertension.
Cholecystectomy is the most frequently performed gastrointestinal surgery in the United States. In this study, we characterized racial disparities in in-hospital mortality after cholecystectomy among patients with and without decompensated cirrhosis. All patients who underwent cholecystectomy between 1998 and 2003 were queried from the Nationwide Inpatient Sample, the largest population-based and geographically representative all-payer database of hospital discharges in the United States. Crude mortality among races was determined for those with and without cirrhosis with portal hypertension and subsequently adjusted for demographic and clinical factors. In-hospital mortality associated with cholecystectomy was higher in the portal hypertensive group compared with those without portal hypertension (10.8% vs 1.4%; P < .0001). African Americans had greater adjusted mortality risk than whites in both the nonportal hypertensive (odds ratio [OR], 1.48; 95% CI, 1.35-1.63) and portal hypertensive (odds ratio [OR], 2.37; 95% CI, 1.47-3.84) groups, although the mortality gap was more pronounced in the latter. For portal hypertensive patients, undergoing cholecystectomy at a liver transplant center was associated with dramatically lower mortality (OR, 0.41; 95% CI, 0.25-0.69). In-patient mortality after cholecystectomy is 7.8-fold higher in patients with portal hypertension compared with those without portal hypertension. African Americans experienced higher mortality than whites after cholecystectomy, especially in the presence of portal hypertension. Cholecystectomy at a liver transplant center may offer survival benefit for patients with portal hypertension.
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Percutaneous Impella Recover circulatory support in high-risk coronary angioplasty.
Due to the increased life expectancy derived from better conditions of life and improved medical technology, interventional cardiologists are facing challenging procedures in older and much more delicate patients, in whom percutaneous coronary intervention is generally considered less dangerous than cardiac surgery. We present two recent cases of high-risk complete myocardial revascularization in patients older than 80 years assisted by the Impella Recover 2.5. In our initial experience this device proved to be relatively easy to set up and hemodynamically useful for patients with left ventricular dysfunction and end-stage coronary atherosclerosis.
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Adverse neonatal outcomes: examining the risks between preterm, late preterm, and term infants.
There is a relative paucity of data regarding neonatal outcomes in the late preterm cohort (34 to 36 6/7 weeks). This study sought to assess differences in adverse outcomes between infants delivering 32 to 33 6/7, 34 to 36 6/7 weeks, and 37 weeks or later. Data were collected as part of a retrospective cohort study of preterm labor patients (2002-2005). Patients delivering 32 weeks or later were included (n = 264). The incidence of adverse outcomes was assessed. Significant associations between outcomes and gestational age at delivery were determined using chi(2) analyses and Poisson regression modeled cumulative incidence and controlled for confounders. Late preterm infants have increased risk of adverse outcomes, compared with term infants. Controlling for confounders, there was a 23% decrease in adverse outcomes with each week of advancing gestational age between 32 and 39 completed weeks (relative risk 0.77, P < .001, 95% confidence interval, 0.71-0.84). Further investigation regarding obstetrical management and long-term outcomes for this cohort is warranted.
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South Carolina Partners for Preterm Birth Prevention: a regional perinatal initiative for the reduction of premature birth in a Medicaid population.
The objective of the study was to improve the distribution of preterm deliveries in a Medicaid population through a regional perinatal risk assessment and case management initiative. An innovative public/private partnership was initiated in the 8 county Lowcountry (LC) perinatal region to reduce preterm birth (PTB) among Medicaid recipient women. Eligible women were identified and underwent telephonic risk assessment, education, and access to a 24 hours, 7 days per week perinatal hotline. Women with predetermined risk factors for PTB were offered patient-centered case management. Medicaid claims and birth certificate data were used to compare obstetric outcomes for 2006 (intervention) and 2004 (control) in both the Lowcountry (LC; program) and Midlands (ML; nonprogram) perinatal regions. There were 6356 Medicaid deliveries in the LC in 2006. Of these, 2111 were referred for telephonic risk assessment; 317 had identifiable PTB risk factors and consented to case management. Compared with 2004, there was a significant improvement in the distribution of preterm birth (P = .05) in the LC region, primarily confined to deliveries less than 28 weeks (1.6% vs 1.1%; P = .029, relative risk [RR] 0.75, 95% confidence interval [CI], 0.51-0.96). There were also reductions in the frequency (6.7% vs 5.8%; RR 0.86, 95% CI, 0.75-0.98; P = .04) and mean duration (25.0 vs 20.6 days; 95% CI, 1.03-7.77; P = .01) of neonatal intensive care unit (NICU) admissions. No changes were identified in the ML region. A regional initiative of telephonic risk assessment and case management of Medicaid recipient women significantly reduced deliveries less than 28 weeks and NICU care.
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The outcome of twin-twin transfusion syndrome complicated with placental insufficiency.
The aim was to evaluate the incidence and perinatal outcomes of TTTS complicated with placental insufficiency (PI/TTTS). This was a retrospective study of all TTTS with PI. PI is defined as estimated fetal weight < 10% with elevated head circumference/abdominal circumference ratio and weight discordance > 20%. Fifty-two out of 270 (19%) pregnancies met criteria. Forty-nine (94.2%) donor twins were diagnosed with PI/TTTS. Fifteen were treated with amnioreduction, 26 with selective fetoscopic laser photocoagulation, 4 with donor intrafetal radiofrequency ablation (RFA), and 7 had expectant management. There was a high incidence of abnormal Dopplers and abnormal placental cord insertion in the donor twin (58% marginal, 35% membranous) with a mean estimated fetoscopic donor placental share of 26.1 +/- 14.3%. There was a significant decrease in the overall donor survival rate of 61% (4 RFA selected donors were excluded) as compared to overall recipient survival rate of 85%, respectively (P = .009). There was no significant difference in donor or recipient survival rate among the treatment groups (P = .058). Placental insufficiency impacts the survival of the affected twins in the setting of TTTS. Studies are needed for appropriate treatment in TTTS with placental insufficiency.
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Assessment of some diterpenoids in commercial distilled gin.
In the present study the qualitative and quantitative determination of diterpenoids in commercial distilled gin was carried out. This widely consumed juniper-based spirit is aromatized using Juniper (Juniperus communis) berries. Although juniper reportedly contains several diterpenic compounds, no studies have addressed the diterpenic composition of juniper-based spirits or beverages. With this objective, here we followed a multilevel factorial experimental design to optimize a direct immersion-solid phase microextraction (DI-SPME) method coupled to gas chromatography/mass spectrometry and analyzed eight commercial brands of gin. With total concentrations ranging from 10 to 190 microg L(-1), manool, manoyl oxide and trans-totarol were the most abundant diterpenoids of the 10 identified or tentatively identified at variable but not negligible concentrations in the distilled gin samples. The diterpenic composition allowed the brands to be differentiated. This indicates that these compounds contribute to the sensory characteristics of the distinct commercial brands, thus guaranteeing the authenticity and consequently the quality of the product.
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The effectiveness of inpatient rehabilitation in the acute postoperative phase of care after transtibial or transfemoral amputation: study of an integrated health care delivery system.
To compare outcomes between lower-extremity amputees who receive and do not receive acute postoperative inpatient rehabilitation within a large integrated health care delivery system. An observational study using multivariable propensity score risk adjustment to reduce treatment selection bias. Data compiled from 9 administrative databases from Veterans Affairs Medical Centers. A national cohort of veterans (N=2673) who underwent transtibial or transfemoral amputation between October 1, 2002, and September 30, 2004. Not applicable. One-year cumulative survival, home discharge from the hospital, and prosthetic limb procurement within the first postoperative year. After reducing selection bias, patients who received acute postoperative inpatient rehabilitation compared to those with no evidence of inpatient rehabilitation had an increased likelihood of 1-year survival (odds ratio [OR]=1.51; 95% confidence interval [CI], 1.26-1.80) and home discharge (OR=2.58; 95% CI, 2.17-3.06). Prosthetic limb procurement did not differ significantly between groups. The receipt of rehabilitation in the acute postoperative inpatient period was associated with a greater likelihood of 1-year survival and home discharge from the hospital. Results support early postoperative inpatient rehabilitation following amputation.
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Impact of comorbidities on stroke rehabilitation outcomes: does the method matter?
To examine the impact of comorbidities in predicting stroke rehabilitation outcomes and to examine differences among 3 commonly used comorbidity measures--the Charlson Index, adjusted clinical groups (ACGs), and diagnosis cost groups (DCGs)--in how well they predict these outcomes. Inception cohort of patients followed for 6 months. Department of Veterans Affairs (VA) hospitals. A total of 2402 patients beginning stroke rehabilitation at a VA facility in 2001 and included in the Integrated Stroke Outcomes Database. Not applicable. Three outcomes were evaluated: 6-month mortality, 6-month rehospitalization, and change in FIM score. During 6 months of follow-up, 27.6% of patients were rehospitalized and 8.6% died. The mean FIM score increased an average of 20 points during rehabilitation. Addition of comorbidities to the age and sex models improved their performance in predicting these outcomes based on changes in c statistics for logistic and R(2) values for linear regression models. While ACG and DCG models performed similarly, the best models, based on DCGs, had a c statistic of .74 for 6-month mortality and .63 for 6-month rehospitalization, and an R(2) of .111 for change in FIM score. Comorbidities are important predictors of stroke rehabilitation outcomes. How they are classified has important implications for models that may be used in assessing quality of care.
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Winged scapula caused by a dorsal scapular nerve lesion: a case report.
Dorsal scapular nerve lesions are quite rare. A case of a 51-year-old man who had right shoulder pain, weakness of right arm elevation, and prominence of right scapula for 6 months is presented. The condition had been abruptly developed after lifting a heavy box overhead on which he felt a sharp pain in the right shoulder. On clinical examination, there was a prominence of the lower medial border and inferior angle of the right scapula compared with the left. In addition, the right scapula was located more lateral. Magnetic resonance imaging of the thorax revealed the presence of a thinner rhomboid major muscle with a pathologic signal compared with the other side. Needle electromyography of the right rhomboid muscle revealed a long duration, polyphasic motor unit potential with reinnervation potentials, and spontaneous activity. According to these findings, the patient was diagnosed as having a winged scapula because of dorsal scapular nerve lesion.
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Radiological appearances of papillary breast lesions.
This review illustrates the varied appearances of benign and malignant papillary breast tumours, as identified by a breast cancer-screening programme. The commonest mammographic appearance of a papillary tumour is as a soft-tissue mass, with calcification present in less than half of cases. When calcification is present the pattern is variable, but clusters of pleomorphic calcification can occur, sometimes resembling the mammographic appearance of invasive ductal carcinoma. Ultrasonography of papillary lesions typically shows a solid, oval, intraductal mass, often associated with duct dilatation. A cystic component is also commonly seen, and lesions may appear hypervascular on colour Doppler ultrasound. Magnetic resonance imaging (MRI) has a high sensitivity, but low specificity for detecting papillary tumours, and is useful in establishing the extent and distribution of lesions in patients with multiple papillomatosis. Despite a benign histology on core biopsy, an argument exists for complete surgical excision of all papillary tumours, as a significant proportion of papillomas will contain foci of atypia or overt malignant change.
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Sieving a living: a review of the biology, ecology and conservation status of the plankton-feeding basking shark Cetorhinus maximus.
The basking shark Cetorhinus maximus is the world's second largest fish reaching lengths up to 12 m and weighing up to 4 tonnes. It inhabits warm-temperate to boreal waters circumglobally and has been the subject of fisheries exploitation for at least 200 years. There is current concern over its population levels as a consequence of directed harpoon and net fisheries that in the north-east Atlantic Ocean alone took over 100,000 mature individuals between 1946 and 1997. As a consequence, it is not known whether populations are recovering or are at a fraction of their historical, pre-fishing biomass. They are currently Red-listed as vulnerable globally, and endangered in the north-east Atlantic. The basking shark is one of only three shark species that filter seawater for planktonic prey and this strategy dominates key aspects of its life history. Until recently, very little was known about the biology, ecology and behaviour of this elusive species. The advent of satellite-linked electronic tags for tracking has resulted in considerable progress in furthering our understanding of basking shark behaviour, foraging, activity patterns, horizontal and vertical movements, migrations and broader scale distributions. Genetic studies are also beginning to reveal important insights into aspects of their global population structure, behaviour and evolutionary history. This chapter reviews the taxonomy, distribution and habitat, bionomics and life history, behaviour, population structure, exploitation, management and conservation status of the basking shark. In doing so, it reveals that whilst important behavioural and ecological information has been gained, there are still considerable gaps in knowledge. In particular, these relate to the need to resolve population sizes, spatial dynamics such as population sub-structuring and sexual segregation, the critical habitats occupied by pregnant females, and the distribution and scale of fishery by-catch rates. Although challenging, it is arguable that without achieving these goals the conservation status of the basking shark will be difficult to assess accurately.
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Hormonal influences on seizures: basic neurobiology.
There are sex differences and effects of steroid hormones, such as androgens, estrogens, and progestogens, that influence seizures. Androgens exert early organizational and later activational effects that can amplify sex/gender differences in the expression of some seizure disorders. Female-typical sex steroids, such as estrogen (E2) and progestins, can exert acute activational effects to reduce convulsive seizures and these effects are mediated in part by the actions of steroids in the hippocampus. Some of these anticonvulsive effects of sex steroids are related to their formation of ligands which have agonist-like actions at gamma-aminobutyric acid (GABAA) receptors or antagonist actions at glutamatergic receptors. Differences in stress, developmental phase, reproductive status, endocrine status, and treatments, such as anti-epileptic drugs (AEDs), may alter levels of these ligands and/or the function of target sites, which may mitigate differences in sensitivity to, and/or tolerance of, steroids among some individuals. The evidence implicating sex steroids in differences associated with hormonal, reproductive, developmental, stress, seizure type, and/or therapeutics are discussed.
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Epilepsy in women: special considerations for adolescents.
Adolescence is a time of many changes. It is a time of growing independence, physical and emotional change, accompanied by social insecurity. Girls tend to enter puberty ahead of their male peers, growing and changing physically. Our culture tells adolescents that they are still immature, but their bodies are saying otherwise. The adolescents are also becoming aware of themselves as individuals, separate from their parents, and are presented with the challenges of independent thinking and action. If, in the midst of all of these changes, an adolescent is given the diagnosis of a chronic disease such as epilepsy, there is an additional burden. Often the adolescent must go through a variety of emotions, including shame, denial, anger, and sadness. Our role as medical providers is to provide some perspective to the illness and help guide our adolescent patient through the tumultuous emotions of grieving and acceptance. We must provide a foundation of assistance and emotional support, as well as medical knowledge. With a firm but compassionate hand, we can help them cope with their disorder. In this chapter, Drs. Haut and Zupanc explore some of the unique considerations in adolescent women with epilepsy. The first part of the chapter deals with the epidemiologic diagnosis of epilepsy in adolescence, the effect of epilepsy on reproductive health, hormonal influences on epilepsy (including catamenial seizures), and the effects of antiepileptic drugs (AEDs) on hormones, contraception, and bone health. In the second part of the chapter, we deal with the very real psychosocial issues and comorbidities of epilepsy, including quality of life, school performance, depression, migraine headaches, social stigma, and lifestyle changes. In the final section, the authors suggest strategies for clinical patient management.
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Sexual dysfunction in women with epilepsy: role of antiepileptic drugs and psychotropic medications.
Sexual dysfunction is a frequently encountered comorbid disorder in patients with neurological and psychiatric disorders. Importantly, sexual dysfunction can also occur as a treatment emergent adverse effect of a number of commonly used psychotropic and antiepileptic medications, and can include decreased libido, erectile dysfunction, disordered arousal, delayed orgasm, and anorgasmia. These effects can occur in both men and women, and can be seen across age groups. Understanding the neurobiology of normal sexual response, as well as the pharmacologic mechanisms of these commonly used medications can enable the clinician to predict how medication use may impact different phases of sexual response. Discussion of the current treatment strategies for female sexual dysfunction is also elucidated in this chapter.
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Laser therapies for glaucoma: new frontiers.
Glaucoma is a long-term ocular neuropathy defined by optic disc or retinal nerve fiber structural abnormalities and visual-field defects. Treatment for glaucoma consists of reducing intraocular pressure (IOP) to an acceptable target range to prevent further optic-nerve damage. Currently available treatments include topical drug (single then multidrug combinations) followed, for those patients on maximal tolerated medical therapy who still need additional IOP reduction, by laser treatments. These included laser iridotomy, laser trabeculoplasty, laser iridoplasty, laser cyclophotocoagulation. Although the various types of laser enjoyed great success as glaucoma therapy for many years, recently the excimer laser trabeculotomy is a promising IOP-lowering technique.
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Modern aqueous shunt implantation: future challenges.
The aqueous shunts that are currently available are based on the principles of the Molteno implant, i.e., a permanent sclerostomy, routing of aqueous to the equatorial subconjunctival space, and an end plate to prevent obstruction, and also to determine the surface area for absorption. While the Ahmed Glaucoma Valve appears to have improved the predictability of early intraocular pressure (IOP) control, the Baerveldt Glaucoma Implant has a tendency towards a lower rate of long-term excessive encapsulation. As a result of improvements in predictability, shunts are used more widely. Because of these positive factors, and ongoing concerns regarding the bleb-related problems associated with mitomycin C trabeculectomy, there is an increasing interest in the use of shunts as primary surgical management for primary glaucoma. At present, the main barrier to wider use of shunts in less-complicated glaucomas will probably be the unknown long-term effect on corneal endothelium, an issue that has not yet been properly addressed.
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Anomalous palmar cutaneous branch of the median nerve in the distal forearm: case report.
Variations exist in the anatomy of the palmar cutaneous branch of the median nerve about the wrist. We report an anatomic variation in the course of the palmar cutaneous branch of the median nerve identified in a 17-year-old girl undergoing surgery for a scaphoid nonunion. Instead of coursing ulnar to the flexor carpi radialis tendon, deep to the antebrachial fascia between the tendons of the flexor carpi radialis and palmaris longus, the palmar cutaneous branch of the median nerve was noted to cross volar to the distal aspect of the flexor carpi radialis to lie on its radial aspect. Knowledge of the anatomic variant described in this report should encourage surgeons to dissect carefully as they expose the flexor carpi radialis during the exposure of the distal radius or scaphoid.
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Desmoplastic fibroma of the hand: case report.
Desmoplastic fibroma is a benign tumor of the soft tissue and rarely of the bone. It typically presents in the trunk and proximal limbs, but it is quite rare in the hands. We present a rare case of desmoplastic fibroma of the soft tissues of the hand that presented as a slow-growing, painless, well-encapsulated mass.
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Dipeptidyl peptidase-4 as a new target of action for type 2 diabetes mellitus: a systematic review.
Type 2 diabetes mellitus is a metabolic disease leading to microvascular and macrovascular complications including coronary artery disease and stroke. Management of diabetes has been challenging, particularly in the presence of the enormous prevalence of obesity. In recent years, various inhibitors of the enzyme dipeptidyl peptidase (DPP)-4 have been developed to treat diabetes. The enzyme DPP-4 cleaves incretins, which, among other functions, stimulate insulin and suppresses glucagon. Inhibition of this enzyme results in an increase in the half-life and the sustained physiologic action of incretins, leading to an improvement in hyperglycemia. One such agent, namely sitagliptin (MK-04,310), has been introduced into the United States market, and another agent, vildagliptin (LAF237), is being used in Europe and elsewhere. This article is intended to evaluate the effectiveness of DPP-4 inhibitors as a therapeutic modality for managing type 2 diabetes. The authors conducted a literature search of various databases to identify the clinical trials involving the DPP inhibitors and concluded that the DPP-4 inhibitors, for example, sitagliptin and vildagliptin, are efficacious for managing diabetes as monotherapy or combination therapy.
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Putative golden proportions as predictors of facial esthetics in adolescents.
In orthodontics, facial esthetics is assumed to be related to golden proportions apparent in the ideal human face. The aim of the study was to analyze the putative relationship between facial esthetics and golden proportions in white adolescents. Seventy-six adult laypeople evaluated sets of photographs of 64 adolescents on a visual analog scale (VAS) from 0 to 100. The facial esthetic value of each subject was calculated as a mean VAS score. Three observers recorded the position of 13 facial landmarks included in 19 putative golden proportions, based on the golden proportions as defined by Ricketts. The proportions and each proportion's deviation from the golden target (1.618) were calculated. This deviation was then related to the VAS scores. Only 4 of the 19 proportions had a significant negative correlation with the VAS scores, indicating that beautiful faces showed less deviation from the golden standard than less beautiful faces. Together, these variables explained only 16% of the variance. Few golden proportions have a significant relationship with facial esthetics in adolescents. The explained variance of these variables is too small to be of clinical importance.
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Image distortion and spatial resolution of a commercially available cone-beam computed tomography machine.
Our objective was to evaluate images produced by a commercially available cone-beam computed tomography (CBCT) machine (i-CAT model 9140-0035-000C, Imaging Sciences International, Hatfield, Pa) for measurement and spatial resolution (ie, the ability to separate 2 objects in close proximity in the image) for all settings and in all dimensions. A custom phantom containing 0.3 mm diameter chromium metal markers approximately 5 mm apart in 3 planes of space was developed for analyzing distortion and measurement accuracy. This phantom was scanned in the CBCT machine by using all 12 commercially available settings. The distance between the markers was measured 3 times on the 3-dimensional images by using a Digital Imaging and Communications in Medicine (DICOM) viewer and was also measured 3 times directly on the phantom with a fine-tipped digital caliper. A line-pair phantom was used to evaluate spatial resolution. Thirty evaluators analyzed images and assigned a resolution from 0.2 to 1.6 mm according to the separation of the line pairs. There were no statistically significant differences among the 3-dimensional images for any setting, in any dimension, or in images divided by thirds in terms of measurement accuracy. Comparison of the CBCT measurements to the direct digital caliper measurements showed a statistically significant difference (P <0.01). However, the absolute difference was <0.1 mm and is probably not clinically significant for most applications. The worst spatial resolution found was 0.86 mm. Spatial resolution was lower at faster scan times and larger voxel sizes. This CBCT machine has clinically accurate measurements and acceptable resolution.
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