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Identification and characterization of errors and incidents in a medical intensive care unit.
To assess the frequency, type, consequences, and associations of errors and incidents in a medical intensive care unit (ICU). Two-hundred and sixteen consecutive patients with predominantly cardiovascular and pulmonary disorders admitted between December 2002 and February 2003 were enrolled. Demographic data, SAPS II, and TISS-28 were obtained for all patients. Prior to patient enrolment all staff members (physicians, nurses, physiotherapists) were repeatedly encouraged to make use of the Incident Report Form (IRF) and detailed descriptions on how, why and when to use the IRF were provided. During the observation period of 64 days, 50 errors involving 32 patients (15%) were reported. Patients subjected to errors were more severely ill (SAPS II 42 +/- 25 vs. 32 +/- 18, P < 0.05), had a higher hospital mortality (38% vs. 9%), and a longer ICU stay (11 +/- 18 vs. 3 +/- 5 days, P < 0.05). Gender, age and TISS-28 were equally distributed. Each day of ICU stay increased the risk by 8% (odds ratio 1.078, 95% confidence interval 1.034-1.125, P < 0.001), and by 2.3% per SAPS II point (odds ratio 1.023, 95% confidence interval 1.006-1.040, P < 0.001). The majority of errors and incidents were judged as 'human failures' (73%), and 46 errors and incidents (92%) as 'avoidable'. The identification and characterization of errors and incidents combined with contextual information is feasible and may provide sufficient background information for areas of quality improvement. Areas with a high frequency of errors and incidents need to undergo process evaluation to avoid future occurrence. | {
"pile_set_name": "PubMed Abstracts"
} |
Transient azomethine-ylides from a stable amino-carbene and an aldiminium salt.
Catalytic amounts of a protic reagent such as tert-butyl alcohol promote the isomerization of a stable amino-aryl-carbene into a transient azomethine ylide. Deprotonation of an alkyl-aldiminium salt also leads to a transient azomethine ylide, but labeling experiments rule out the transient formation of the corresponding amino-alkyl-carbene. The potential hypersurface between model amino-carbene, aziridine, and azomethine ylide is investigated. | {
"pile_set_name": "PubMed Abstracts"
} |
Dosimeter placement in the Rando phantom.
Each section of the Alderson Rando phantom contains a tissue-equivalent plastic coating layer approximately 2 mm thick, applied to both faces. This compensates for material removed in the sawing process. Conventional use of thermoluminescent dosimeters positions them totally or partially within the coating layer. Analysis shows that, in the lung region, dosimeters placed in this layer received a dose averaging 39% lower than those placed at midsection. Where bony structures interfere, some dosimeters in the coating layer received an 18% higher dose than those at midsection. Therefore, positioning dosimeters at the center of a section is recommended. | {
"pile_set_name": "PubMed Abstracts"
} |
Safety outcomes in meta-analyses of phase 2 vs phase 3 randomized trials: Intracranial hemorrhage in trials of bolus thrombolytic therapy.
Recent studies have reported disagreement between meta-analysis of small trials and subsequent large trials addressing the same question. However, disagreement for uncommon but serious adverse safety outcomes has not been examined. To explore disagreement for serious adverse safety (intracranial hemorrhage [ICH]) and efficacy outcomes between meta-analysis of phase 2 (small) vs meta-analysis of phase 3 (large) randomized controlled trials comparing the efficacy of bolus thrombolytic therapy with infusion for acute myocardial infarction (AMI). Electronic databases (MEDLINE, Cochrane Database of Clinical Trials) between January 1980 and December 1999 using the search terms thrombolysis, thrombolytic therapy, and myocardial infarction; conference proceedings; and reference lists. Fifteen randomized trials comparing thrombolytic agents administered by bolus injection with standard infusion therapy in patients with AMI. Data on ICH, other causes of stroke, total mortality, and reinfarction were independently extracted from each study by 2 observers. Meta-analysis of 9 phase 2 trials (n = 3956) revealed a lower risk of ICH with bolus thrombolytic therapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.27-1.01), which was not statistically significant. Meta-analysis of 6 phase 3 trials (n = 62 673) indicated a significant increase in risk of ICH (OR, 1.25; 95% CI, 1.06-1.49). These results were significantly different (P =.01). There was no disagreement for efficacy outcomes. Phase 2 trials included younger and heavier patients with lower baseline blood pressures, and were more often open-label. Subgroup analyses suggested that each of these factors was associated with a lower estimate of risk of ICH with bolus agents. Our results suggest that when therapeutic interventions are associated with a potential for uncommon but serious adverse safety outcomes, there may be differences between small phase 2 and large phase 3 trials that result in their disagreement for safety but not necessarily efficacy outcomes. Further investigation of the frequency and causes of disagreement between small and large trials for safety outcomes is warranted. | {
"pile_set_name": "PubMed Abstracts"
} |
Preoperative assessment of anterolateral thigh flap cutaneous perforators by colour Doppler flowmetry.
An anterolateral thigh flap is very useful in head and neck reconstruction because of its long and large-caliber vascular pedicle, large skin territory and elevation simultaneous with tumour resection. However, the number and locations of cutaneous perforators vary individually, and thus, it is not widely used because flap elevation is often complicated and time-consuming owing to unexpected anatomical variations. To overcome this disadvantage, we assessed the number and locations of cutaneous perforators preoperatively by colour Doppler flowmetry. These data were compared with the intraoperative anatomical findings and their reliability evaluated. A total of 48 cutaneous perforators were found by preoperative colour Doppler flowmetry scanning of 17 anterolateral thigh flaps. All the perforators except two were found intraoperatively. Doppler scanning failed to detect four perforators. Colour Doppler flowmetry assessment therefore has a 92% true-positive rate and a 95.8% positive predictive value. All the flaps except one included multiple perforators, and sufficient blood circulation was observed in all cases. No flaps were unexpectedly changed to anteromedial thigh flaps or contralateral anterolateral thigh flaps because of inappropriate cutaneous perforators or the absence of perforators. Though this investigation is relatively time-consuming (30-40 min) and requires skill, it is very useful for preoperative flap planning and increases the reliability and safety of elevating an anterolateral thigh flap. | {
"pile_set_name": "PubMed Abstracts"
} |
Spotlight on Tdap₅ vaccine (Covaxis®) as a single-booster immunization for the prevention of tetanus, diphtheria, and pertussis: in children (aged ≥4 years), adolescents, and adults.
Covaxis® (also licensed as Triaxis® or Adacel® in individual countries) is a Tdap₅ (i.e. combined tetanus toxoid, reduced diphtheria toxoid, five component acellular pertussis [namely detoxified pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3]) vaccine for the prevention of diphtheria, tetanus, and pertussis. It is approved for use in Europe as a single intramuscular booster dose in children (aged ≥4 years), adolescents, and adults, and in the US it is approved for use in individuals aged 11-64 years. In large, randomized, controlled clinical trials conducted in the UK and North America, a single intramuscular booster dose of Covaxis® induced robust immune responses for all of its component antigens when given to children (aged ≥4 years), adolescents, and adults. In addition, Covaxis® vaccine was safe and generally well tolerated in terms of solicited and unsolicited local injection-site and systemic adverse events, most of which were of mild intensity and resolved without sequelae. Furthermore, the immunogenicity of each individual component and the reactogenicity of Covaxis® vaccine in children, adolescents, and adults was generally similar to that of comparator vaccines. Despite being a vaccine-preventable disease and having >90% primary vaccination coverage worldwide, pertussis remains uncontrolled, particularly amongst adolescents and adults. Given the changing epidemiology of pertussis and the requirement to reduce infection in adolescents and adults (including healthcare workers) and thereby prevent transmission of the disease from these individuals to very young infants, the new 'cocoon strategy' recommended in current vaccination guidelines has become a key strategy in the management of morbidity and mortality associated with pertussis. This strategy focuses on the immunization of healthcare workers, and the parents and family members of infants who are too young to have undergone primary immunization, so as to prevent the transmission of pertussis to these young at-risk infants. The implementation of the 'cocoon strategy' may finally give countries the ability to control pertussis infections in these at-risk infants and ultimately provide the desired herd immunity against pertussis. In line with this strategy, a booster dose of Covaxis® vaccine provides a valuable option to reduce pertussis morbidity and mortality, and to maintain seroprotection against diphtheria and tetanus in children (aged ≥4 years), adolescents, and adults. | {
"pile_set_name": "PubMed Abstracts"
} |
Anterior cruciate ligament bundle measurement by MRI.
An accurate in vivo method of measuring dimensions of the anteromedial (AM) and posterolateral (PL) anterior cruciate ligament (ACL) bundles has not been established. The purpose of this study was to measure each individual bundle using double oblique axial MR imaging of the ACL, to compare this with cadaveric measurements, and to investigate the range of measurements seen in normal subjects. In five cadaveric knees, measurements obtained of the proximal, middle, and distal segments of each ACL bundle from double oblique axial MR images were compared with direct measurements following anatomical dissection. Thereafter, the size of both bundles from 24 normal knees was measured using an identical MR technique. Inter-observer variation was calculated using intraclass correlation. ACL bundle measurement in the cadaveric knees had a strong correlation (r = 0.93) with measurements obtained following anatomical dissection. No significant difference existed between measurements obtained from cadaveric knees and living normal subjects (p > 0.05). Interobserver correlation for MR measurements was excellent (R = 0.92-0.93). Overall, the long and short axis of the AM bundle were significantly larger than those of the PL bundle (p < 0.05). Also, men showed significantly larger AM and PL bundles than women (p < 0.05). Bundle size was not related to age or knee dominance. The individual ACL bundles can be accurately measured on double oblique axial MR imaging. The AM bundle is larger in caliber than the PL bundle. Both bundles are larger in men than in women and there is no significant side-to side difference. | {
"pile_set_name": "PubMed Abstracts"
} |
Lewis acid catalyzed intramolecular Diels-Alder reactions of acyclic (Z)-substituted 1,3-dienes.
Lewis acid catalyzed intramolecular Diels-Alder reactions of trienes (E,E,Z)-1a-d, (E,E,Z)-4a-d, and (E,Z,Z)-7a,b are described. Trienes containing enal or enone dienophiles cyclize in excellent yield under mild conditions using substoichiometric amounts of MeAlCl(2), in most cases with high levels of diastereoselectivity. The thermal IMDA reactions of 1a, 4a, and 7a require forcing conditions and proceed in low yield with reversed stereoselectivity in the cases of 1a and 4a. | {
"pile_set_name": "PubMed Abstracts"
} |
Racial differences in young children's blood pressure. Responses to dynamic exercise.
Studies have observed that black children exhibit greater blood pressure increases in response to dynamic exercise than white children. Seventy-five (51 white, 24 black) children aged 4 to 6 years old had their blood pressure and heart rate measured before, during, and 5 minutes after dynamic upright exercise on the treadmill. Girls had higher preexercise heart rate values than the boys, and showed a marginally slower recovery of diastolic blood pressure values. Black children had significantly lower preexercise and peak exercise heart rate values, higher systolic blood pressure values at peak exercise, and greater systolic blood pressure increases in response to exercise than did white children. These differences are discussed in terms of mechanisms that may be responsible for racial differences in essential hypertension. | {
"pile_set_name": "PubMed Abstracts"
} |
Functional analysis of the c-myb proto-oncogene.
Targeted mutagenesis studies were initiated to determine the normal biological function of the c-myb proto-oncogene. While heterozygous mice are phenotypically indistinguishable from their wild-type littermates, homozygous mutant fetuses die at approximately 15.5 days of gestation apparently due to anemia, which results from an inability to switch from embryonic yolk sac to fetal liver erythropoiesis. Studies are currently being done to determine the extent of hematopoietic abnormalities in the homozygous mutant fetuses. In vitro assays for hematopoietic colony-forming cells have been used to determine the frequency of both erythroid and myeloid progenitors in the fetal livers of wild-type, heterozygous, and homozygous mutant c-myb fetuses. The reduced number of erythroid progenitors was not unexpected considering the mutant fetus's pale color and reduced hematocrit. The dramatically reduced number of colonies derived from myeloid progenitors in the mutant fetuses in comparison to the number detected in phenotypically normal littermates suggests that expression of the c-myb proto-oncogene is critical for the proliferation and/or differentiation of early hematopoietic progenitors and possibly hematopoietic stem cells. Other possible explanations would include a hematopoietic progenitor migration problem from the yolk sac to the fetal liver or a defect in the microenvironment of the liver. Whether the lymphoid lineage is also adversely affected by the lack of c-myb expression remains to be determined. RT-PCR and Northern blot analyses were used in an attempt to identify downstream genes which may be directly or indirectly regulated by the Myb gene product. While the levels of expression of several genes involved in erythropoiesis (GATA-1, NF-E2, SCL, and EpoR) were reduced in the livers of homozygous mutant fetuses in comparison to phenotypically normal littermates and one gene, Kit ligand (KL), was expressed at higher levels in the mutant livers, these results must be viewed with caution. The livers of the mutant fetuses have been shown to be hypocellular in comparison to those of phenotypically normal littermates (35). It is possible that the Myb gene product is directly or indirectly modulating the expression of these genes. Conversely, the alteration in expression may be due to the reduced number or absence of specific hematopoietic lineages in the livers of the mutant fetuses. Differential display has also been used to identify putative novel genes that are involved in hematopoiesis. Preliminary studies suggest that this may be a powerful methodology to compare the expression pattern of genes in the fetal liver of wild-type, heterozygous, and homozygous mutant littermates at 14.5 days of gestation. To date nearly 60% of the partial cDNAs subcloned analyzed have been shown to be differentially expressed. More importantly, 75% of the differentially expressed cDNAs that have been sequenced appear to encode novel genes. Whether any of these novel genes are involved in the c-myb transcriptional cascade remains to be determined. Overall, analysis of the c-myb mutant fetuses have provided valuable insight into the biological function of this interesting proto-oncogene. The continued analysis of this resource will undoubtedly provide additional information concerning the role of the c-myb gene in hematopoiesis. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of stable xenon in room air on regional cerebral blood flow and electroencephalogram in normal baboons.
Measurement of regional cerebral blood flow (rCBF) was performed in 6 healthy baboons during ventilation with 35% stable xenon in artificial air. rCBF was measured with the intraarterial xenon-133 method. EEG was recorded continuously. All CBF areas of interest over one hemisphere reacted in the same way. Mean flow increased during short-term exposure to stable xenon and decreased if stable xenon inhalation was continued for at least 24 minutes. EEG showed a decrease of alpha- and beta-wave patterns a short time after the start of stable xenon inhalation without further changes over the period when rCBF finally decreased. CO2 reactivity increased in most animals, and autoregulation to mild arterial hypotension was significantly impaired with increased flow. It is concluded that 35% stable xenon in artificial air increases rCBF after short-term exposure and decreases rCBF after longer exposure. EEG changes were noted after short-term exposure. rCBF and EEG recovered rapidly after the end of stable xenon inhalation. | {
"pile_set_name": "PubMed Abstracts"
} |
Enhanced catalytic activity of α-FeOOH-rGO supported on active carbon fiber (ACF) for degradation of phenol and quinolone in the solar-Fenton system.
A new heterogeneous solar-Fenton catalyst, α-FeOOH-reduced graphene oxide (rGO) supported on active carbon fiber (ACF), was synthesized via in situ electrophoretic deposition in a self-assembly process. Optimization of the components (electrophoretic deposition time of GO and Fe, GO dosages), the effect of pH and the catalysts stability were investigated systematically. The results indicated that rGO-α-FeOOH composite is formed during the ferrous-ion-induced self-assembly process on ACF. FeOOH-rGO/ACF displayed excellent catalytic activity for degrading phenol and quinoline under the solar-driven photo-Fenton process in a wide range of pH values (4.5-9.5) and possess good stability in neutral condition. The phenol oxidation process on this catalyst was described by a pseudo-first-order kinetics model. Both the ACF support and solar irradiation promoted greater H2O2 decomposition and produced more OH radicals, thus, significantly improving the catalytic capacity. The introduction of graphene improved the catalytic capacity of the catalyst under solar irradiation. The optimal electrophoretic deposition time of GO and the optimal Fe and initial GO content in deposition were 10 min, 9.8 wt% and 15.0 wt%, respectively. The degradation pathways of phenol and quinoline in the solar-driven photo-Fenton process were also elucidated. | {
"pile_set_name": "PubMed Abstracts"
} |
EWS/ETS fusion genes induce epithelial and neuroectodermal differentiation in NIH 3T3 fibroblasts.
Ewing's sarcoma is the least differentiated member of the peripheral primitive neuroectodermal (pPNET) tumor family. Chromosomal translocations involving the EWS gene and five different Ets family transcription factor genes create fusion genes encoding aberrant transcription factors and are implicated in the vast majority of Ewing's sarcoma cases. Here, NIH 3T3 fibroblasts were infected with control (tk-neo or RAS) and two different EWS/ETS-expressing retroviruses. In vitro studies of established polyclonal lines expressing the two EWS/ETS genes, either EWS/FLI1 or EWS/ETV1, showed induction of cytokeratin 15 gene expression. Both fusion genes also caused characteristic gross morphologic, histologic, and ultrastructural changes in NIH 3T3 cells when transformed cell lines were injected into CB-17-scid mice. Native NIH 3T3 cells with a spindled cell morphology were converted to polygonal cells with high nucleo-cytoplasmic ratios that continued to express abundant cytokeratin. Extracellular collagen deposition was abolished, rough endoplasmic reticulum was markedly diminished, and rudimentary cell-cell attachments appeared. Most strikingly, neurosecretory-type dense core granules like those seen in pPNET were now evident. This murine model, created in mesenchyme-derived NIH 3T3 cells, demonstrated new characteristics of both neuroectodermal and epithelial differentiation and resembled small round cell tumors microscopically. | {
"pile_set_name": "PubMed Abstracts"
} |
Features of stabbing, cough, exertional and sexual headaches in a Turkish population of headache patients.
The aim of this study was to determine the features and prevalence of primary stabbing headache, primary exertional headache, primary headache associated with sexual activity, and primary cough headache in a Turkish population of headache patients. The data for this study were obtained from 245 patients with headache. Of these patients, 55 fulfilled the International Classification of Headache Disorders (second edition) diagnostic criteria for 'other primary headaches' such as primary stabbing headache (n=31), primary cough headache (n=1), primary exertional headache (n=13), primary headache associated with sexual activity (n=4), and both primary cough headache and primary exertional headache (n=6). Primary stabbing headache was found in 12.6% of patients, primary cough headache in 0.4%, primary exertional headache in 5.3% and primary headache associated with sexual activity in 1.6%. | {
"pile_set_name": "PubMed Abstracts"
} |
Structural Plasticity in Adulthood with Motor Learning and Stroke Rehabilitation.
The development of advanced noninvasive techniques to image the human brain has enabled the demonstration of structural plasticity during adulthood in response to motor learning. Understanding the basic mechanisms of structural plasticity in the context of motor learning is essential to improve motor rehabilitation in stroke patients. Here, we review and discuss the emerging evidence for motor-learning-related structural plasticity and the implications for stroke rehabilitation. In the clinical context, a few studies have started to assess the effects of rehabilitation on structural measures to understand recovery poststroke and additionally to predict intervention outcomes. Structural imaging will likely have a role in the future in providing measures that inform patient stratification for optimal outcomes. | {
"pile_set_name": "PubMed Abstracts"
} |
Specific and shared antigenic components of Taenia saginata oncospheres.
Taenia saginata oncosphere components were analysed by double diffusion. Antigenic components in saline or detergent (Triton x-100) extracts of T saginata oncospheres were identified using a rabbit polyclonal serum directed against the oncosphere and compared with extracts prepared from the metacestodes and proglottids of T saginata and six other helminths commonly found in cattle. There were seven antigenic components found in the saline extract of the oncospheres, of which six were shared with the metacestodes and proglottids. None of these components was consistently different from those of the other six helminths. However, one of the four components in the detergent extract of the oncospheres was present in neither of the extracts of other stages of T saginata nor in extracts of other helminths. This may be of diagnostic significance. | {
"pile_set_name": "PubMed Abstracts"
} |
Framework for assessment and monitoring of amphibians and reptiles in the Lower Urubamba region, Peru.
Populations of amphibians and reptiles are experiencing new or increasing threats to their survival. Many of these threats are directly attributable to human activity and resource development. This presents the increasing need for worldwide amphibian and reptile assessments and effective, standardized monitoring protocols. Adaptive management techniques can assist managers in identifying and mitigating threats to amphibian and reptile populations. In 1996, Shell Prospecting and Development, Peru initiated a natural gas exploration project in the rainforest of southeastern Peru. The Smithsonian Institution's Monitoring and Assessment of Biodiversity Program worked closely with Shell engineers and managers to establish an adaptive management program to protect the region's biodiversity. In this manuscript, we discuss the steps we took to establish an adaptive management program for amphibian and reptile communities in the region. We define and outline the conceptual issues involved in establishing an assessment and monitoring program, including setting objectives, evaluating the results and making appropriate decisions. We also provide results from the assessment and discuss the appropriateness and effectiveness of protocols and criteria used for selecting species to monitor. | {
"pile_set_name": "PubMed Abstracts"
} |
The diagnosis of blocked cerebrospinal fluid shunts: a prospective study of referral to a paediatric neurosurgical unit.
A prospective study was undertaken of all children referred to the Hospital for Sick Children with a provisional diagnosis of shunt blockage over a 5-month period. Fifty-two admissions were recorded, relating to 45 children, 5 of whom had multiple admissions. Only 19 of the 52 admissions led to a final diagnosis of shunt malfunction. No source of referral, whether by the child's general practitioner or from another hospital, was found to be more accurate than direct referral by the parents to the neurosurgical ward. Headache, vomiting and irritability were not significant indicators as to whether the child's shunt was actually blocked, and nor was the duration of the symptoms. Drowsiness was a significant, but not definite, indicator of shunt blockage, while pyrexia made it more likely that the patient had an alternative diagnosis. In 35 of the admissions a computed tomographic scan was performed: a normal scan, unchanged from previous scans, did not reliably exclude the diagnosis of shunt blockage. Percutaneous manometry via the reservoir of the shunt system was performed during 26 admissions: this investigation produced no false positives nor false negatives, but was equivocal in 5 cases, all of which were found at surgery to have a definite shunt blockage. The accuracy of the diagnosis of shunt blockage made prior to referral to a neurosurgical unit is discussed, together with the implications for resource use. | {
"pile_set_name": "PubMed Abstracts"
} |
Repolarization of the presynaptic action potential and short-term synaptic plasticity in the chick ciliary ganglion.
Stimulation-induced increases in synaptic efficacy have been described as being composed of multiple independent processes that arise from the activation of distinct mechanisms at the presynaptic terminal. In the chick ciliary ganglion, four components of short-term synaptic plasticity have been described: F1 and F2 components of facilitation, augmentation, and potentiation. In the present study, intracellular recording from the presynaptic calyciform nerve terminal of the chick ciliary ganglion revealed that the late repolarization and afterhypolarization (AHP) phases of the presynaptic action potential are affected by repetitive stimulation and that the time course of these effects parallel that of facilitation. The effects of these changes in the presynaptic action potential time course on calcium influx were tested by using the recorded action potential waveforms as voltage command stimuli during whole-cell patch-clamp recordings from acutely isolated chick ciliary ganglion neurons. The "facilitated" action potential waveform (slowed repolarization, decreased AHP amplitude) evoked calcium current with slightly but significantly greater total calcium influx. Taken together, these results are consistent with the hypothesis that activity-dependent changes in the presynaptic action potential are one of several mechanisms contributing to the facilitation phase of stimulation-induced increases in transmitter release in this preparation. | {
"pile_set_name": "PubMed Abstracts"
} |
Three years experience of adults admitted to hospital in north-east Scotland with E. coli O157.
To describe the epidemiology, clinical features, treatment and outcomes of adults with E. coli O157 infection presenting to Aberdeen Royal Infirmary over a three year period. A retrospective casenote review. Thirty-two confirmed cases of E. coli O157 infection were admitted between 1997 and 2000. The median age was 58 years (range 16-93). Ten patients (31%) were from the city of Aberdeen and 22 (69%) from surrounding rural areas. Twenty-seven patients (85%) presented between May and October. The source of infection was unknown or unconfirmed in all cases. Bloody diarrhoea was present in 30 (94%). Leucocytosis was present in 18 (63%) but only four patients (13%) had a fever. Six of the 32 patients (19%) developed Haemolytic-Uraemic Syndrome (HUS) of whom 2 died. Ten patients received antibiotics of whom two developed HUS. Twenty-seven of the 32 (85%) had made a full recovery by time of discharge, three (9%) had impaired renal function and two (6%) died in hospital. E. coli O157 infection tends to occur sporadically in rural areas in North East Scotland. It is not usually associated with fever. Infection occurs more commonly in the summer and autumn. HUS complicates infection in almost one fifth of patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Therapeutic value of Ginkgo biloba in reducing symptoms of decline in mental function.
The Chinese tree Ginkgo biloba or "maiden hair tree" is extensively cultivated for the exploitation of the medicinal properties of its leaves. From these, a well-defined extract designated "EGb 761" has been developed, which was commercialized initially as Tanakan, Tebonin and Rokin; a similar product, Kaveri (LI 3170), also exists. The major therapeutic applications for these products are "cerebral insufficiency", other cerebral disorders, neurosensory problems and peripheral circulatory disturbances. Four primary concepts of action have been proposed to explain the pharmacotherapeutic benefits of EGb761; these are: vasoregulatory, cognition-enhancing, stress-alleviating, and gene-regulatory. These actions are believed to be realized through the principal active ingredients, flavonoids and the terpenoids ginkgolides and bilobalide acting simultaneously in concert, combination and synergy, so-called polyvalent action. It has been proposed that EGb761 may improve the memory of healthy volunteers, and in an assessment of [corrected] forty clinical studies, it was reported that Ginkgo was able to improve the twelve different symptoms comprising 'cerebral insufficiency', all of which are manifest in the elderly. These were supported in a second major study, using LI1370. However, in both instances, the evidence was largely based upon the results of self-assessment questionnaires. Latterly, in a large double blind study of men and women with the diagnosis of uncomplicated dementia who were administered Ginkgo for a year, a further positive outcome was claimed. In this study, patients were tested using ADAS-cog, GERRI and CGIC. It is suggested that whilst these different outcomes are compatible with (but do not affirm) a clinical benefit resulting from the use of Ginkgo, the application of a more objective system of assessment would be able to provide firm proof. It is proposed, therefore, that an objective, computer-based testing system for assessment of clinical improvement in volunteers and patients administered Ginkgo (such as CANTAB) would provide the convincing evidence currently being sought by patients, carers, physicians, legislators and the pharmaceutical industry. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effect of hydrocortisone on the concentration of serotonin and monoamine oxidase activity in the vascular tract of the eye].
Effect of hydrocortisone on content of serotonin was studied in eye vascular tract or blood and the monoamine oxidase (MAO) activity was estimated in eye vascular tract of young and adult rabbits at various periods after administration of hydrocortisone under conjunctiva. After administration of hydrocortisone content of serotonin was increased in eye vascular tract and decreased in blood. Maximal serotonin reaction was observed in vascular tract of adult rabbits within 24 hrs after the hydrocortisone treatment and in one-month-old rabbits--within 4-6 hrs. In blood of adult animals the most distinct decrease in serotonin content was found within 4-6 hrs after the single administration of the preparation; in one-month-old rabbits the effect was observed after the repeated treatment within 7 days. Effect of hydrocortisone on the MAO activity in eye vascular tract varied depending on the age. In one-month-old rabbits the MAO activity was increased distinctly within 24 hrs after single administration of the preparation and in adult animals the enzyme activity was decreased within 4-6 hrs and did not alter at the other periods after the hydrocortisone administration. | {
"pile_set_name": "PubMed Abstracts"
} |
An Evaluation of the Automated Cobas u 701 Microscopy Analyzer for the Routine Screening of Urine to Identify Negative Samples.
Urinalysis based on microbiological culture and manual microscopy requires expertise and is labor intensive. Automated screening could save time and improve patient management in clinical settings. We evaluated the fully automated cobas u 701 analyzer for identifying infection-negative urine samples using 2,046 anonymized samples from a routine pathology laboratory. Samples containing ≥ 40 white blood cells (WBC)/µL and/or ≥ 100 bacteria/µL were considered positive. For microbiological cultures: pure growth of ≥ 108 colony-forming units (cfu)/L was considered significant; > 107 cfu/L was considered significant for pregnant women, children < 12 years, immune-compromised/critical care patients or patients with > 100 WBC/µL. The cobas u 701 analyzer identified 1,346 positive samples, giving a 65.7% culture rate. Sensitivity and negative predictive value were high (> 99%). Most replicates were within two standard deviations of the original measurement. The cobas u 701 analyzer is an effective screening tool for routine urinalysis and demonstrates rapid turnaround times, thus benefiting patients and clinicians. | {
"pile_set_name": "PubMed Abstracts"
} |
Apolipoprotein E-deficient mice created by systemic administration of antisense oligodeoxynucleotides: a new model for lipoprotein metabolism studies.
Atherosclerotic cardiovascular disease results from complex interactions among multiple genetic and environmental factors. Thus, it is important to elucidate the influence of each factor on cholesterol metabolism. For this purpose, transgenic/gene-targeting technology is a powerful tool for studying gene functions. However, this technology has several disadvantages such as being time consuming and expensive. Accordingly, we established new animal models using in vivo gene transfer technology. In this study, we examined the feasibility of the creation of a new animal model for the study of atherosclerosis. We hypothesized that apolipoprotein (apo) E-deficient mice can be created by systemic administration of antisense apo E oligodeoxynucleotides (ODN) coupled to the HVJ-liposome complex. Initially, we examined the localization and cellular fate of FITC-labeled antisense ODN administered intravenously. FITC-labeled ODN transfection by the HVJ-liposome method resulted in fluorescence in the liver, spleen and kidney, but not in other organs such as brain. Moreover, fluorescence with the HVJ-liposome method was sustained for up to 2 weeks after transfection, which resulted in a striking difference from transfection of ODN alone or ODN in liposomes without HVJ, which showed rapid disappearance of fluorescence (within 1 day). Given these unique characteristics of the HVJ-liposome method, we next examined transfection of antisense apo E ODN by intravenous administration. Transfection of antisense apo E ODN resulted in a marked reduction of apo E mRNA levels in the liver, but no change in apo B and beta-actin mRNA levels. In mice fed a normal diet, a transient increase in cholesterol and triglyceride levels was observed in the antisense apo E-treated group, but they returned to normal levels by 6 days after transfection. Similar findings were also found in mice fed a high cholesterol diet. Neither scrambled nor mismatched ODN resulted in any increase in cholesterol. To make chronic hypercholesterolemic mice, we therefore performed repeated injections of apo E antisense ODN. Whenever antisense apo E ODN were injected, mice showed a transient increase in cholesterol and triglyceride. Cumulative administration of antisense apo E ODN resulted in a sustained increase in cholesterol for up to 3 weeks after the last transfection. Finally, mice treated with repeated injections of antisense apo E every week developed sustained hypercholesterolemia and hypertriglyceridemia until withdrawal of injections. Apolipoprotein-deficient mice created by intravenous administration of antisense ODN are a promising new animal model to help understand the role of apolipoprotein in vivo and develop a new drug therapy targeting apolipoprotein. | {
"pile_set_name": "PubMed Abstracts"
} |
The vasodilator--beta-blocker interaction--some determinants of its clinical success.
A number of structurally dissimilar compounds, sharing the ability to induce vasodilatation have come into clinical usefulness as antihypertensive drugs. Their successful utilisation often depends critically on an appropriate combination with diuretics and beta-blockers. Beta-blockers can specifically inhibit the reflex cardiac stimulation which otherwise may limit the tolerability and haemodynamic value of these drugs. A synergistic antihypertensive effect has been demonstrated with hydrallazine and propranolol and possibly exists with other combinations. Generally, vasodilators are not first-line drugs in chronic therapy but are best added to beta-blockers. Variations of the dose-response and the time-course of effect are stressed as being important determinants of a successful interaction. | {
"pile_set_name": "PubMed Abstracts"
} |
Enhancement of radiosensitivity of lung adenocarcinoma using a decoction from the Fuzhengzengxiao formula.
To study the effects of a decoction of Fuzhengzengxiao formula on lung adenocarcinoma regarding the inflammatory protein S100A9 known to enhance cancer cell sensitivity. A nude mouse model of human lung adenocarcinoma was established. The mice were randomly divided into four groups using the random number table method: Group I, control; Group II, treatment with a decoction of the Fuzhengzengxiao formula alone; Group III, treatment with radiotherapy alone; and Group IV, treatment with radiotherapy plus a decoction of Fuzhengzengxiao formula. When the tumor body was 1 cm3 in diameter, the tumor bearing mice in Groups III and IV were irradiated at a single dose of 10 Gy and the tumor inhibition rate was evaluated. The expression of S100A9 was determined using Western blotting and q-PCR (Real-time Quantitative PCR Detecting System). The sensitivity of cells containing RNAi S100A9 to radiotherapy was evaluated using the Click multiple target model,and the cell cycle was analyzed using flow cytometry. Relative to the control group, the expression of S100A9 in the tumors in each treatment group was decreased, especially in Group IV. The sensitizing enhancement ratio (SER) Dq was > 1 after RNAi S100A9; it decreased the surviving fraction after a 2 Gy dose exposure,and also the D0 and Dq of the tumor cells; in addition, the radiosensitivity of G2/M cells was significantly increased. The decoction of the Fuzhengzengxiao formula downregulated the expression of S100A9 in lung adenocarcinoma cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Apodized pixel lenses in compact shadow-casting correlators.
We present a compact two-dimensional shadow-casting correlator that can perform correlation between inputs of size 256 × 256 and a point-spread function of size 32 × 32. A two-dimensional array of mutually incoherent sources is used to encode the point-spread function, and each source is individually steered to improve the light uniformity and the light-utilization efficiency. The geometric optics constraint requires that the shadow region be very close to the input plane. This constraint is removed by the introduction of apodized pixel lenses in the input spatial light modulator. The pixel lenses move the shadow plane to their Fourier plane, and pixel apodization reduces the interchannel cross talk, thereby improving the signal-to-noise ratio. Simulation and experimental results verifying these concepts are presented. | {
"pile_set_name": "PubMed Abstracts"
} |
Nitric oxide participates in cataract development in selenite-treated rats.
The role of nitric oxide in the development of selenite-induced cataracts in rats was examined using nitric oxide synthase (NOS) inhibitors. Subcutaneous injection of sodium selenite was used to induce cataracts in rats, with or without pretreatment with NOS inhibitors. The anterior eye segment analysis system (EAS-1000, Nidek) was used to measure lens opacity. The glutathione content of the lenses was determined by an HPLC method and the Ca2+ content by atomic absorption spectrometry. Nitrite, a stable metabolite of nitric oxide, was determined fluorometrically. NADPH-diaphorase activity staining and Western blot analysis were used to determine NOS levels. Administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), inhibited lens opacification in selenite-treated rats. NG-nitro-d-arginine methyl ester, an inactive enantiomer of l-NAME, had no effect. Aminoguanidine, another NOS inhibitor, also inhibited the development of cataracts in a dose-dependent manner. On the other hand, L-arginine, a substrate of NOS, accelerated the development of cataracts. Although the opacification of the lenses was apparent approximately 3 days after selenite injection, the nitrite level was increased within one day. In addition, NOS was induced in the eye within one day of selenite injection. The present study demonstrated that NOS inhibitors prevented the development of cataracts in selenite-treated rats. The results also suggest that nitric oxide had an important role in the development of selenite-induced cataracts. | {
"pile_set_name": "PubMed Abstracts"
} |
[Ultrasonography of the gallbladder and oral cholecystography. A prospective comparative study].
A prospective study comparing the information supplied by ultrasonography of the gallbladder and oral cholecystography was conducted in 254 patients with clinically suspected gallbladder calculi. The results demonstrated the limitations of cholecystography, notably the frequency of non-opacification in the absence of hepatic-biliary tract pathology and the possibility of false-negative results. Ultrasonography proved adequate in more than 80% of the cases and may be considered as the examination of choice for the diagnosis of biliary calculi. Its own limitations are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Changes in alpha motoneuron excitability of the soleus muscle in relation to vestibular stimulation assessed by angular acceleration in man.
Variations in spinal motoneuron excitability, tested by the monosynaptic H reflex of the soleus muscle, were studied in man in relation to angular acceleration of the body in a damped rotating chair. Clockwise and anticlockwise rotation produced similar changes on the same spinal motoneurons, consisting of a first clear-cut facilitatory phase starting at 0.4 degrees of rotation (corresponding to 156 ms) with a peak between 10 and 30 degrees, followed by a second excitatory phase between 50 and 100 degrees; then, the amplitude of the H reflex progressively recovered to its control value. Both facilitatory phases showed a significant decrease by reducing the angular velocity and acceleration. Control experiments ruled out that both the startle reaction of the subject and variations in the somatosensory input during rotation could be responsible for generating the facilitatory effects on the H reflex. The mean value of the voluntary reaction to turning sensation was 1.1 degrees, corresponding to about 335 ms. It is concluded that the changes described in motoneuron excitability could represent a vestibulospinal reflex response originating from the horizontal semicircular canals. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of selenium deficiency on fatty acid metabolism in rats fed fish oil-enriched diets.
The hepatic fatty acid metabolism was investigated in rats stressed by selenium deficiency and enhanced fish oil intake. Changes in the composition of lipids, peroxides, and fatty acids were studied in the liver of rats fed either a Sedeficient (8 microg Se/kg) or a Se-adequate (300 microg Se/kg) diet, both rich in n-3 fatty acid-containing fish oil (100 g/kg diet) and vitamin E (146 mg alpha-tocopherol/kg diet). The two diets were identical except for their Se content. Se deficiency led to a decrease in hair coat density and quality as well as to changes in liver lipids, individual lipid fractions and phospholipid fatty acid composition of the liver. The low Se status did reduce total and reduced glutathione in the liver but did not affect the hepatic malondialdehyde level. In liver phospholipids (PL), Se deficiency significantly reduced levels of palmitic acid [16:0], fatty acids of the n-3 series such as DHA [22:6 n-3], and other long-chain polyunsaturates C-20-C-22, but increased n-6 fatty acids such as linoleic acid (LA) [18:2 n-6]. Thus, the conversion of LA to arachidonic acid was reduced and the ratio of n-6/n-3 fatty acids was increased. As in liver PL, an increase in the n-6/n-3 ratio was also observed in the mucosal total fatty acids of the small intestine. These results suggest that in rats with adequate vitamin E and enhanced fish oil intake, Se deficiency affects the lipid concentration and fatty acid composition in the liver. The changes may be related to the decreased levels of selenoenzymes with antioxidative functions. Possible effects of Se on absorption, storage and desaturation of fatty acids were also discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of phosphorus sources on volatile organic compound emissions from Microcystis flos-aquae and their toxic effects on Chlamydomonas reinhardtii.
There is diverse phosphorus (P) in eutrophicated waters, but it is considered as a crucial nutrient for cyanobacteria growth due to its easy precipitation as insoluble salts. To uncover the effects of complex P nutrients on the emission of volatile organic compounds (VOCs) from cyanobacteria and their toxic effects on other algae, the VOCs from Microcystis flos-aquae supplied with different types and amount of P nutrients were analyzed, and the effects of VOCs and their two main compounds on Chlamydomonas reinhardtii growth were investigated. When M. flos-aquae cells were supplied with K2HPO4, sodium pyrophosphate and sodium hexametaphosphate as the sole P source, 27, 23 and 29 compounds were found, respectively, including furans, sulfocompounds, terpenoids, benzenes, aldehydes, hydrocarbons and esters. With K2HPO4 as the sole P source, the VOC emission increased with reducing P amount, and the maximum emission was found under Non-P condition. In the treatments of M. flos-aquae VOCs under Non-P condition and two main terpenoids (eucalyptol and limonene) in the VOCs, remarkable decreases were found in C. reinhardtii cell growth, photosynthetic pigment content and photosynthetic abilities. Therefore, we deduce that multiple P nutrients in eutrophicated waters induce different VOC emissions from cyanobacteria, and P amount reduction caused by natural precipitation and algal massive growth results in more VOC emissions. These VOCs play toxic roles in cyanobacteria becoming dominant species, and eucalyptol and limonene are two toxic agents. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolation of two contigs of overlapping cosmids derived from human chromosomal band 3p21.1 and identification of 5 new 3p21.1 genes.
Consistent loss of DNA sequences from several regions on the short arm of human chromosome 3 has suggested that multiple tumor suppressor genes reside on chromosome 3p in various types of cancer cells. We have focused our efforts on an analysis of chromosomal band 3p21.1 since aminoacylase-1 (ACY1), which is localized to this band, has been shown to have lower levels of expression in several small cell and non-small cell lung cancer cell lines. Starting with two cosmids within 3p21.1, D3S92 and D3S93, we have isolated two separate contigs of overlapping cosmids within 3p21.1, by screening a library of 5700 chromosome 3-specific cosmid clones. Detailed restriction maps for these two contigs show that they contain multiple clusters of rare cutting restriction endonuclease sites. One contig extends for 100 kb and encompassed both ACY1 and D3S92, and the other extends about 80 kb around the D3S93 locus. Many different restriction fragments derived from these two contigs were found to be evolutionarily conserved and hybridized to distinct message transcripts. These fragments were used to identify homologous cDNAs from an adenogastric cDNA library, and several of these cDNAs were partially sequenced. We have identified five new genes from these two contigs and there is evidence to suggest that several additional genes reside within these cosmid contigs. The genes identified from 3p21.1 were then hybridized to DNA, isolated from a series of lung cancer cell lines and matched normal and tumor DNA from lung cancer patients. No alterations were detected with any of these probes, both at the DNA or RNA levels. A similar analysis with DNA fragments derived from these two genomic regions also failed to detect any alterations. | {
"pile_set_name": "PubMed Abstracts"
} |
Black pine (Pinus nigra) barks as biomonitors of airborne mercury pollution.
Tree barks are relevant interfaces between plants and the external environment, and can effectively retain airborne particles and elements at their surface. In this paper we have studied the distribution of mercury (Hg) in soils and in black pine (Pinus nigra) barks from the Mt. Amiata Hg district in southern Tuscany (Italy), where past Hg mining and present-day geothermal power plants affect local atmospheric Hg concentration, posing serious environmental concerns. Barks collected in heavily Hg-polluted areas of the district display the highest Hg concentration ever reported in literature (8.6mg/kg). In comparison, barks of the same species collected in local reference areas and near geothermal power plants show much lower (range 19-803μg/kg) concentrations; even lower concentrations are observed at a "blank" site near the city of Florence (5-98μg/kg). Results show a general decrease of Hg concentration from bark surface inwards, in accordance with a deposition of airborne Hg, with minor contribution from systemic uptake from soils. Preliminary results indicate that bark Hg concentrations are comparable with values reported for lichens in the same areas, suggesting that tree barks may represent an additional useful tool for biomonitoring of airborne Hg. | {
"pile_set_name": "PubMed Abstracts"
} |
Molecular interactions in poly(ethylene glycol)-water mixtures at various temperatures: density and isentropic compressibility study.
The densities and sound velocities of mixtures of water with poly(ethylene glycol), poly(ethylene glycol) monomethylether, and poly(ethylene glycol) dimethylether with mean molar weights between 250 and 500 have been measured as a function of mixture composition and temperature between 10 and 40 degrees C. Isentropic compressibilities are derived from the data and are compared to those for the ethylene glycol/water system and for other organic solvent/water mixtures. Relative minima in the mixture volume to ideal volume ratio and in the dependence of the compressibility upon mixture composition are discussed in terms of the conformational variability of the chainlike oligomers, of hydrogen-bonded networks, and of water clusters between the oligomer chains. | {
"pile_set_name": "PubMed Abstracts"
} |
Map kinase c-JUN N-terminal kinase mediates PMMA induction of osteoclasts.
Erosive osteolysis induced by implant-derived wear debris is mediated by recruitment and activation of osteoclasts in a pro-inflammatory microenvironment that is enriched with osteoclastogenic and pro-inflammatory cytokines such as RANKL and tumor necrosis factor alpha (TNF-alpha). These cytokines activate the transcription factor NF-kappaB and MAP kinases, including c-Jun, Erks, and p38, all known to be essential for the development of osteoclasts. We have recently documented that TNF and RANKL play a pivotal role in the development of inflammatory osteolysis. We have also found that polymethyl methacrylate (PMMA) particles stimulate osteoclastogenesis, at least in part, by induction of RANKL, TNF, and by activation of NF-kappaB and MAP kinases. More importantly, our data indicate that inhibitors of NF-kappaB and the MAP kinases p38 and ERK abrogate particle-induced osteoclastogenesis. In the current study, we investigated if inhibition of c-Jun N-Terminal kinase (JNK) pathway alters PMMA-induced osteoclastogenesis. Our findings point out that PMMA particles activate the JNK pathway in wild-type and TLR4-null (endotoxin-resistant) osteoclast precursors. This activation was selectively blocked in a dose-dependent fashion by the JNK inhibitor SP600125. Most importantly, we provide evidence that SP600125 inhibits osteoclast formation in a reversible manner. Collectively, our findings demonstrate that activation of the JNK pathway is essential for basal and PMMA-stimulated osteoclastogenesis, and buttress the potential significance of targeting the JNK pathway to inhibit osteolysis. | {
"pile_set_name": "PubMed Abstracts"
} |
The effects of diethyldithiocarbamate on the hepatotoxic action and antitumor activity of N-methylformamide in mice.
The oral administration of diethyldithiocarbamate (DTC) prevented hepatic necrosis induced by N-methylformamide (NMF) in ddY-strain mice, in more susceptible BALB/c mice and in diethylmaleate-treated mice in which NMP-hepatotoxicity was potentiated, as evidenced by suppression of increases of plasma glutamic pyruvic transaminase activity and liver calcium content or by histological observations. Early depletion of liver glutathione following NMF administration was also prevented by DTC. DTC markedly delayed the in vivo metabolism of NMF as indicated by a prolonged retention of plasma and liver NMF levels and an enhancement of urinary excretion of NMF. These observations support a bioactivation mechanism for NMF hepatotoxicity, and the hepatoprotective action of DTC may be due to an inhibition of the metabolic activation of NMF. Hepatotoxic manifestations after repeated administration of NMF also tended to be ameliorated by simultaneous treatment with DTC. Cotreatment with DTC, however, decreased the antitumor activity of NMF against Ehrlich ascites tumors, and Sarcoma 180. This also implies the involvement of a bioactivation mechanism in the antitumor action of NMF, but further studies are necessary to confirm this point. The possible therapeutic value of DTC as a hepatoprotector may be diminished by the suppression of the antitumor activity of NMF. | {
"pile_set_name": "PubMed Abstracts"
} |
Rat LDL metabolism in the perinatal period.
In fetal rats at term LDL carries 75% of the total serum cholesterol, whereas in adult ones this value amounts to 20% only. Using a time-dependent two pool model the flux rates for LDL cholesterol can be calculated for the newborn. The data reveal that at birth the LDL cholesterol flux is 15-20 times higher than in the adult. During the first 2 h of postnatal life the FCR drops down from 0.4 at birth to values measured in the adult. Since at least 75% of LDL is of another origin than VLDL, a direct hepatic LDL synthesis is postulated for the newborn. The liver contributes to about 30% of the total LDL uptake which is mainly realized by a receptor-dependent mechanism, even though the fetus and the newborn exhibit markedly elevated LDL serum concentrations. | {
"pile_set_name": "PubMed Abstracts"
} |
Impact of FDG-labelled positron emission tomography imaging on the management of non-small-cell lung cancer.
Lung cancer is currently the leading cause of cancer-related death in both men and women in most Western countries. Although 5-year survival rates have doubled from 1960s, they are low compared with survival rates for other cancer types. Tumour stage is the strongest prognostic factor and the most important parameter that guides treatment decision making. Metabolic imaging with fluorodeoxyglucose-labelled positron emission tomography (FDG-PET) has proved superior to conventional imaging for staging of non-small-cell lung cancer. This new imaging modality permits more accurate planning of treatment with surgery and radiotherapy and provides information of greater prognostic significance than what can be obtained with conventional approaches. FDG-PET has been approved in the USA and the UK as a basic and invaluable tool in the management of lung cancer. This paper reviews current trends in clinical practice on the applications of FDG-PET in the management of non-small-cell lung cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Challenges in HbA1c Analysis and Reporting in Patients with Variant Hemoglobins.
Hemoglobin A1c (HbA(1)c) is a well-established indicator of mean glycemia. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA(1)c measurements. Variants of hemoglobin especially Hemoglobin E (HbE) is prevalent in South East Asia including Bangladesh. The objective of our study is to compare the HbA(1)c values measured on high performance liquid chromatography (HPLC) and Turbidimetric Inhibition Immunoassay (TINIA) in diabetic patients with variant hemoglobins including HbE. A total of 7595 diabetic patients receiving treatment at BIRDEM General Hospital were analyzed for HbA(1)c results within a period of two months from December 2013 to January 2014. Seventy two cases out of 7595 (0.95%) had either undetectable or below normal HbA(1)c levels (males-33 and females-39; ratio = 0.82:1) by HPLC method. In 34(0.45%) cases, HbA(1)c value was undetectable by HPLC method but was in the reportable range by TINIA method. In the other 38 (0.55%) cases, HbA(1)c levels were below the reportable range (<4%) by HPLC method but were in the normal or higher range by TINIA method. TINIA method did not agree with HPLC method on Bland Altman plot in the 38 cases with below normal HbA(1)c levels, [Mean bias -5.2(-9.3 to 1.0), 95% CI] but agreed very well [mean bias -0.21 (-0.84 to 0.42), y=1.1037+0.776X; r(2)=0.30, p<0.01] in controls. In control group mean MCV was 83.80±7.48 and in study group was 73.65±10.44. Alkaline electrophoresis confirmed the variant hemoglobin to be HbE. The fasting blood sugar levels of all the 72 cases correlated strongly with TINIA method (r(2) =0.75, p<0.0001) but not with HPLC (r = 0.24, p=0.13). In our regions where populations have a high prevalence of Hb variant, proper knowledge of hemoglobin variants which affect the measurements HbA(1)c level is essential. MCV of 80fl or below may serve as a rough guide to select samples that require analysis by TINIA method. Moreover, HPLC may be a convenient and inexpensive tool for screening of hemoglobinopathies especially among diabetic population in Bangladesh. It may therefore be helpful in improving management of complications related to both anaemia and iron overload. | {
"pile_set_name": "PubMed Abstracts"
} |
Role of latent TGF-beta 1 binding protein in vascular remodeling.
Transforming growth factor-beta (TGF-beta) is secreted as a latent, high molecular weight complex, which is composed of TGF-beta, a latency associated peptide (LAP) and a latent TGF-beta binding protein (LTBP). In this study, we report on the role of LTBP in vascular remodeling. 0.01-5 ng/ml of LTBP stimulated the migration activities of cultured rat arterial smooth muscle cells (SMC) about 4-7 fold compared with control in vitro. The maximal activity of SMC migration by LTBP was 75% of that by 10 ng/ml of PDGF-BB. A checker board analysis showed that the migration by LTBP was chemotactic, not chemokinetic. By cross-linking experiment, LTBP associated with 80-120 kd cell surface protein of SMC, suggesting that a part of LTBP can bind with SMC. Furthermore, LTBP was more strongly expressed in the intimal layer than in the medial layer of BCI artery. These results suggest that LTBP plays an important role in the initial stage of arterial intimal thickening through the acceleration of SMC migration from the medial to intimal layer and is one of the essential factors influencing vascular remodeling. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of amitriptyline on GABA-stimulated 36CI- uptake in relation to a behavioral model of depression.
The dominant-submissive relationship established between two rats competing for food is a model of depression and is used here to divide animals into two behaviorally distinct groups. Basal and GABA-stimulated 36CI- uptake was investigated for both dominant and submissive rats as well as the in vitro effect of the antidepressant amitriptyline (AMI). Because the antidepressant action of AMI only appears after chronic treatment, the effect of chronic injections of AMI on these behavioral and biochemical measures was also studied. Basal 36CI- uptake is significantly higher for dominant rats than for submissive rats. Increasing concentrations of AMI added to membrane vesicles enhanced 30 microM GABA-stimulated chloride uptake for dominant rats and inhibited it for submissive rats. Chronic treatment of dominant and submissive rats with AMI reversed these in vitro effects. The biochemical data correspond to the changes of the rats behavior in the dominance test after chronic treatment with AMI. However, this correlation is more clear for dominant than for submissive rats. Specific chloride influx was used as a measure of the sensitivity of GABAA receptor to GABA. This revealed different sensitivity states for GABAA receptors in tissues obtained from dominant and submissive rats. It is possible that the distinct conformational states of GABAA receptor are responsible for differences in rats behavior and in vitro effects of AMI before and after in vivo treatment of rats with this anti-depressant. | {
"pile_set_name": "PubMed Abstracts"
} |
"HPV effect" in the female lower genital tract. A community study.
To determine the distribution of "human papillomavirus (HPV) effect" and intraepithelial neoplasia in the lower female genital tract in one community with a prospective study. In a family practice setting, colposcopy was offered to all women presenting for a routine cervical cytologic smear. Directed biopsies were taken from areas staining abnormally with acetic acid or iodine. This study of 224 women showed a high incidence of HPV effect in the lower genital tract (68%), including 18% on the vulva. The age distribution suggests a coital influence. A five-year review showed persistence of HPV effect on the vulva or vagina in only one patient. One other woman developed cervical intraepithelial neoplasia (CIN) 1. HPV effect is common in the lower genital tract of women under the age of 30 years. Colposcopic study suggested that HPV effect on the vulva and vagina is transient. The relatively high incidence of HPV effect on the vulva may explain why cervical HPV and CIN generally appear only after coitarche, as a consequence of physical transfer. This may help explain why women with a single lifetime sexual partner are not exempt from the risk of cervical cancer or its precursors. | {
"pile_set_name": "PubMed Abstracts"
} |
Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly(butyl cyanoacrylate) nanoparticles.
We have synthesized novel cationic poly(butyl) cyanoacrylate (PBCA) nanoparticles coated with chitosan, formulation of curcumin nanoparticles. The size and zeta potential of prepared curcumin nanoparticles were about 200 nm and +29.11 mV, respectively with 90.04% encapsulation efficiency. The transmission electron microscopy (TEM) study revealed the spherical nature of the prepared nanoparticles along with confirmation of particle size. Curcumin nanoparticles demonstrate comparable in vitro therapeutic efficacy to free curcumin against a panel of human hepatocellular cancer cell lines, as assessed by cell viability (3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay [MTT assay]) and proapoptotic effects (annexin V/propidium iodide staining). In vivo, curcumin nanoparticles suppressed hepatocellular carcinoma growth in murine xenograft models and inhibited tumor angiogenesis. The curcumin nanoparticles' mechanism of action on hepatocellular carcinoma cells is a mirror that of free curcumin. | {
"pile_set_name": "PubMed Abstracts"
} |
The future role of health centers in improving national health.
International health rankings for the US are heavily influenced by striking racial and socioeconomic health status disparities. Current discussions of health determinants frequently relegate or entirely dismiss health care contributions despite increasing evidence of the importance of access to primary care. Health centers deliver community-based primary care to a considerable and growing proportion of the nation's most vulnerable and have produced significant health improvements, especially for women and children. Policies that disproportionately benefit those in greatest need are likely to produce the largest gains in national health. Continued expansion of the health center network to ensure primary care for those who remain underserved is both an effective and politically acceptable strategy to improve national health. | {
"pile_set_name": "PubMed Abstracts"
} |
Gene expression in inherited breast cancer.
Large proportions of hereditary breast cancers are due to mutations in the two breast cancer susceptibility genes BRCA1 and BRCA2. Considerable effort has gone into studying the function(s) of these tumor suppressor genes, both in attempts to better understand why individuals with these inherited mutations acquire breast (and ovarian) cancer and to potentially develop better treatment strategies. The advent of tools such as cDNA microarrays has enabled researchers to study global gene expression patterns in, for example, primary tumors, thus providing more comprehensive overviews of tumor development and progression. Our recent study (Hedenfalk et al., 2001) strongly supports the principle that genomic approaches to classification of hereditary breast cancers are possible, and that further studies will likely identify the most significant genes that discriminate between subgroups and may influence prognosis and treatment. A large number of hereditary breast cancer cases cannot be accounted for by mutations in these two genes and are believed to be due to as yet unidentified breast cancer predisposition genes (BRCAx). Subclassification of these non-BRCA1/2 breast cancers using cDNA microarray-based gene expression profiling, followed by linkage analysis and/or investigation of genomic alterations, may help in the recognition of novel breast cancer predisposition loci. To summarize, gene expression-based analysis of hereditary breast cancer can potentially be used for classification purposes, as well as to expand upon our knowledge of differences between different forms of hereditary breast cancer. Initial studies indicate that a patient's genotype does in fact leave an identifiable trace on her/his cancer's gene expression profile. | {
"pile_set_name": "PubMed Abstracts"
} |
Mouse skin photosensitivity with dihaematoporphyrin ether (DHE) and aluminium sulphonated phthalocyanine (AlSPc): a comparative study.
Skin photosensitivity of sun exposed sites is the major side effect of dihaematoporphyrin ether (DHE) photodynamic therapy (PDT). Reports of severe oedema and erythema have generally been anecdotal. We have studied aluminium sulphonated phthalocyanine (AlSPc) as a potential photosensitiser for PDT. In this paper we report our work comparing the skin photosensitivity reactions of DHE and AlSPc. We have studied: (i) the time course of the skin reactions, (ii) the effect of increasing time from administration of photosensitiser to irradiation, (iii) drug-skin reaction dose response. Groups of Skh I female hairless albino mice were given an intravenous bolus dose of either 0.9% saline solution, AlSPc or DHE (Photofrin II). Drug doses ranged from 0.5 to 50 mg/kg. At times ranging from 1 h to 1 month animals were irradiated with a range of doses of solar simulated radiation (SSR). The skin reaction was observed over a 2 week period. DHE reactions were always more severe than those with AlSPc. Peak skin reaction was seen at 3 h for DHE and 6 h for AlSPc. DHE reactions were still visible 2 weeks after irradiation whereas the AlSPc reaction disappeared by 48 h. Irradiation evoked a reaction up to 2 months after administration of DHE but only up to 2 weeks with AlSPc. The mean SSR dose at which a skin reaction was seen decreased with increasing dose of both agents. The rate of decrease was slower with AlSPc than DHE. This study suggests that in PDT, AlSPc will cause much less skin photosensitivity than DHE. | {
"pile_set_name": "PubMed Abstracts"
} |
[Characteristics of the action of an acidic sulfated polysaccharide on global blood coagulation in vitro. Preliminary study in various species of mammals and in man].
An acid sulphated polysaccharide, isolated from a red marine seaweed, Asparagopsis armata ( Harv .), increases the coagulation time of the plasma in vitro studies. This property, compared with the anticoagulant activity of pentosan polysulphate and heparin, pr esents , with concentration and temperature, some variations in man and other mammals . The rat and human plasma seem to behave in the same way with this substance. | {
"pile_set_name": "PubMed Abstracts"
} |
Negative mammograms in symptomatic patients with breast cancer.
To determine the limitations of mammography in symptomatic patients. Approximately 20,000 mammograms obtained during a 2-year period were correlated with the results of a retrospective review of the pathology database, which revealed 711 patients with breast cancer. A total of 496 of these patients underwent mammography at the authors' institution. Three observers reviewed the mammograms of patients with "normal" mammograms within 6 months of excisional biopsy. The parenchymal patterns were also assessed. Mammographic abnormalities were identified in 481 cases (97%), and 15 mammograms (3%) were interpreted as "unremarkable." Fourteen of the unremarkable cases were available for review, which indicated nine true-negative findings, one technical error, two observer errors, and two combined technical and observer errors. The technical error involved the lower inner quadrant of the breast, adjacent to the chest wall. All 14 mammograms were of dense breasts. Mammographic abnormalities were identified in nearly all patients with proved breast cancer. Mammograms in which lesions were missed were of dense breasts, but one-third of the lesions were visible in retrospect. When examining symptomatic patients with dense breasts, radiologists should use optimal mammographic techniques and consider using nonmammographic breast imaging modalities. | {
"pile_set_name": "PubMed Abstracts"
} |
A study of mortality in workers engaged in the mining, smelting, and refining of nickel. I: Methodology and mortality by major cause groups.
Following the publication of the NIOSH nickel criteria document in 1977, the Joint Occupational Health Committee of the International Nickel Company (INCO) commissioned a mortality study of the company's Ontario workforce. This paper describes the detailed methodology and primary mortality results of the ensuing study; subsequent papers will describe more detailed findings of cause-specific mortality. An historical prospective mortality study of approximately 54,000 INCO workers has been conducted. Men with six months or more of service were followed for mortality during a 35-year period by computerized record linkage to the Canadian National Mortality Data Base. From a company-provided list of men known to have died and through independent follow-up of a random sample of 1,000 subjects of unknown status, we estimate a mortality ascertainment rate of 95%. Cause-specific standardized mortality ratios calculated with respect to Ontario provincial mortality rates indicate an excess of accidental deaths in men working in the Sudbury area and an excess of cancer deaths at the company's Port Colborne nickel refinery. A strong healthy worker effect was found for both all-disease mortality ad cancer mortality. The lower than expected mortality persisted for about 15 years beyond initial hiring. | {
"pile_set_name": "PubMed Abstracts"
} |
Bilateral giant hydroureteronephrosis--a case report with a review of the literature.
Giant hydronephrosis and hydroureteronephrosis are rare conditions, but must be kept in mind in especially children and in young-to-middle-aged adults with long-standing, often symptomless, enlargement of the abdomen. A case of bilateral giant hydroureteronephrosis due to calculi in the ureters is reported. Despite renal insufficiency the patient denied any treatment, but survived 42 months after the primary diagnosis. For diagnostic purposes intravenous pyelography, ultrasonography and computerized tomography are preferable. Supplementary ante- and retrograde pyelography is valuable in locating stenosis or calculi. | {
"pile_set_name": "PubMed Abstracts"
} |
Association of regional racial/cultural context and socioeconomic status with arthritis in the population: a multilevel analysis.
To examine the extent to which differences in individual- and regional-level socioeconomic status and racial/cultural origin account for geographic variations in the prevalence of self-reported arthritis, and to determine whether regional characteristics modify the effect of individual characteristics associated with reporting arthritis. Analyses were based on the 2000-2001 Canadian Community Health Survey (>15 years, n = 127,513). Arthritis was self-reported as a long-term condition diagnosed by a health professional. A 2-level logistic regression model was used to identify predictors of reporting arthritis. Individual-level variables included age, sex, income, education, immigration status, racial/cultural origin, smoking, physical activity, and body mass index. Regional-level variables included the proportion of low-income families, low education, unemployment, recent immigrants, Aboriginals, and Asians. At the individual level, age, sex, low income, low education, Aboriginal origin, current smoking, and overweight/obesity were positively associated with reporting arthritis; recent immigration and Asian origin were negatively associated with reporting arthritis. At the regional level, percentages of low-income families and the Aboriginal population were independently associated with reporting arthritis. Regional income and racial/cultural origin moderated the effects of individual income and racial/cultural origin; low-income individuals residing in regions with a higher proportion of low-income families reported arthritis more than low-income individuals living in better-income regions. Both individual and regional factors were found to contribute to variations in the prevalence of arthritis, although significant unexplained variation remained. Further research is required to better understand the mechanisms that underlie these regional effects and to identify other contributing factors to the remaining variation. | {
"pile_set_name": "PubMed Abstracts"
} |
Source partitioning using stable isotopes: coping with too many sources.
Stable isotopes are increasingly being used as tracers in environmental studies. One application is to use isotopic ratios to quantitatively determine the proportional contribution of several sources to a mixture, such as the proportion of various pollution sources in a waste stream. In general, the proportional contributions of n+1 different sources can be uniquely determined by the use of n different isotope system tracers (e.g., delta13C, delta15N, delta18O) with linear mixing models based on mass balance equations. Often, however, the number of potential sources exceeds n+1, which prevents finding a unique solution of source proportions. What can be done in these situations? While no definitive solution exists, we propose a method that is informative in determining bounds for the contributions of each source. In this method, all possible combinations of each source contribution (0-100%) are examined in small increments (e.g., 1%). Combinations that sum to the observed mixture isotopic signatures within a small tolerance (e.g., +/-0.1 per thousand ) are considered to be feasible solutions, from which the frequency and range of potential source contributions can be determined. To avoid misrepresenting the results, users of this procedure should report the distribution of feasible solutions rather than focusing on a single value such as the mean. We applied this method to a variety of environmental studies in which stable isotope tracers were used to quantify the relative magnitude of multiple sources, including (1) plant water use, (2) geochemistry, (3) air pollution, and (4) dietary analysis. This method gives the range of isotopically determined source contributions; additional non-isotopic constraints specific to each study may be used to further restrict this range. The breadth of the isotopically determined ranges depends on the geometry of the mixing space and the similarity of source and mixture isotopic signatures. A sensitivity analysis indicated that the estimated ranges vary only modestly with different choices of source increment and mass balance tolerance parameter values. A computer program (IsoSource) to perform these calculations for user-specified data is available at http://www.epa.gov/wed/pages/models.htm. | {
"pile_set_name": "PubMed Abstracts"
} |
Previous experience of induced abortion as a risk factor for fetal death and preterm delivery.
As part of a community-based study in Korea to evaluate the effects of previous induced abortion on length of gestation and pregnancy outcome of subsequent pregnancies, we analyzed data obtained from January 1979 to December 1981 on pregnancies reported to family health workers in Kang Hwa Island, Korea. The preterm, live-birth rates were not significantly associated with previous induced abortion. Overall, the life table-estimated fetal death rate for women enrolled at the eighth or earlier weeks of gestation was 13.7%, 10.2% for women with no previous induced abortion and 28.9% for women with previous induced abortion. The relative risk for fetal death for women who had undergone a previous abortion was 2.8; relative risk for parous women compared to nulliparous women was 3.4. After controlling for parity, previous induced abortion was not a significant variable for fetal death rate. | {
"pile_set_name": "PubMed Abstracts"
} |
Current and future strategies for the treatment of malignant brain tumors.
Glioblastoma (GB) is the most common subtype of primary brain tumor in adults. These tumors are highly invasive, very aggressive, and often infiltrate critical neurological areas within the brain. The mean survival time after diagnosis of GB has remained unchanged during the last few decades, in spite of advances in surgical techniques, radiotherapy, and also chemotherapy; patients' survival ranges from 9 to 12 months after initial diagnosis. In the same time frame, with our increasing understanding and knowledge of the physiopathology of several cancers, meaningful advances have been made in the treatment and control of several cancers, such as breast, prostate, and hematopoietic malignancies. Although a number of the genetic lesions present in GB have been elucidated and our understanding of the progressions of this cancer has increased dramatically over the last few years, it has not yet been possible to harness this information towards developing effective cures. In this review, we will focus on the classical ways in which GB is currently being treated, and will introduce a novel therapeutic modality, i.e., gene therapy, which we believe will be used in combination with classical treatment strategies to prolong the life-span of patients and to ultimately be able to control and/or cure these brain tumors. We will discuss the use of several vector systems that are needed to introduce the therapeutic genes within either the tumor mass, if these are not resectable, or the tumor bed, after successful tumor resection. We also discuss different therapeutic modalities that could be exploited using gene therapy, i.e., conditional cytotoxic approach, direct cytotoxicity, immunotherapy, inhibition of angiogenesis, and the use of pro-apoptotic genes. The advantages and disadvantages of each of the current vector systems available to transfer genes into the CNS are also discussed. With the advances in molecular techniques, both towards the elucidation of the physiopathology of GB and the development of novel, more efficient and less toxic vectors to deliver putative therapeutic genes into the CNS, it should be possible to develop new rationale and effective therapeutic approaches to treat this devastating cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Chronic conditions in elders in assisted living facilities: associations with daily functioning, self-assessed health, and depressive symptoms.
The increasing life expectancy of older adults has prompted an increase in chronic conditions that may interfere with their daily living and impact physical and mental health. This study examined associations between commonly reported chronic conditions, daily functioning, self-assessed health, and depressive symptoms of elders. A secondary analysis of existing data from 314 elderly residents of 29 facilities was conducted. The most frequently reported conditions were arthritis (64%), hypertension (47%), and heart problems (35%). Elders who reported having all three of these most frequently reported conditions differed significantly from those who reported none or one of the three conditions (p<.001) on their perception of interference with daily functioning and self-assessed health. Although differences on depressive symptoms were found between groups defined by number and combinations of conditions, specific trends in the data were not detected. Elder's rating of interference of their chronic conditions on daily functioning was moderately associated with their self-assessed health (r=-.50, p<.001) and depressive symptoms (r=.41, p<.001). While chronic conditions may be unavoidable, assessing their comorbidity in elders is important for developing interventions to preserve their daily functioning and promote their optimal health. | {
"pile_set_name": "PubMed Abstracts"
} |
Studies of the plasma kinin-forming system in cirrhosis of the liver.
Kininogen level, that of active kinins and kininase activity in the plasma of patients suffering from cirrhosis of the liver and of healthy people were studied. The kininogen content was determined by different available methods i.e. the trypsin and acetone techniques and by means of the plasma and glandular kallikrein preparation. An increase in kininase activity and a lowered kininogen level as determined by all the methods were found in the sick persons. The maximal decrease in the kininogen level determined by means of the plasma kallikreins is substantiated in connection with the increased fibrinolytic activity of the plasma of the patients with hepatic cirrhosis. | {
"pile_set_name": "PubMed Abstracts"
} |
[Changes in the spatiotemporal pattern of urbanization in Erdos of Inner Mongolia and related driving forces].
Urbanization is the most drastic form of land use change, which affects the biodiversity and ecosystem functioning and services far beyond the limits of cities. Based on the land use data in three time periods and by the method of landscape pattern analysis, this paper analyzed the change characteristics of the spatiotemporal pattern of urbanization in the four Banners of East Erdos at different spatial scales. Urbanization had profound effects on the local ecology, society, and economics. The landscape as a whole became more fragmented and complex, and different patch types exhibited distinctive spatial characteristics and were affected to different degrees at class-level. Desert and urban land varied greater, and cropland was most affected by urbanization. Resources factors, increase of urban population, and development of economy were the main socio-economic driving factors to the changes in the local landscape spatiotemporal pattern of urbanization. | {
"pile_set_name": "PubMed Abstracts"
} |
Three-stranded clip of the oligonucleotide 5'-(dT)10pO(CH2CH2O)3p(dT)10pO(CH2CH2O)3p(dA)10-3'.
Temperature dependence of UV and CD spectra of the oligonucleotide 5'-(dT)10-L-(dT)10-L-(dA)10-3' [tripl(ATT)] [L = -pO(CH2CH2O)3p-] in phosphate buffer, pH 7, at various NaCl concentrations and in the presence or absence of 0.01 M MgCl2 has been studied. At low oligonucleotide concentrations (2.2 x 10(-5) M nucleotide concentration) all structural transitions proceed intramolecularly. Tripl(ATT) exists in three forms: as a three-stranded clip (at low temperatures), a double-stranded hairpin (at intermediate temperatures), and as an open strand (at high temperatures). Thermodynamic parameters of the triplex formation depending on the NaCl concentration were calculated. The CD spectra were assigned to the single-, double-, and three-stranded forms. Ethidium bromide (EtBr) binding to the three-stranded clip was studied. Ethidium bromide molecules were shown to intercalate into the triple helix with the stable complex formation (association constant is 10(6)). One molecule of three-stranded clip binds not more than three EtBr molecules. The proposed synthetic model (oligonucleotide blocks coupled by hydroxyalkyl chains) has been shown to be convenient for studies of the physical and chemical properties of the triplex and other multistranded complexes of DNA. | {
"pile_set_name": "PubMed Abstracts"
} |
Case for diagnosis: (Ectodermal dysplasia: Christ-Siemens-Touraine syndrome).
Christ-Siemens-Touraine syndrome (hypohidrotic ectodermal dysplasia) is a rare syndrome characterized by the triad of absent or reduced sweating, hypotrichosis, and defective dentition. The prominent forehead, saddle nose, thick lower lip and pointy chin produce a distinctive facies. The full syndrome only occurs in men as it is an X-linked recessive condition. | {
"pile_set_name": "PubMed Abstracts"
} |
Diabetes, but Not Hypertension and Obesity, Is Associated with Postoperative Cognitive Dysfunction.
Older people undergoing surgery are at risk of developing postoperative cognitive dysfunction (POCD), but little is known of risk factors predisposing patients to POCD. Our objective was to estimate the risk of POCD associated with exposure to preoperative diabetes, hypertension, and obesity. Original data from 3 randomised controlled trials (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis on diabetes, hypertension, baseline blood pressure, obesity (BMI ≥30 kg/m2), and BMI as risk factors for POCD in multiple logistic regression models. Risk estimates were pooled across the 3 studies. Analyses totalled 1,034 patients. POCD occurred in 5.2% of patients in DECS, in 9.4% in SuDoCo, and in 32.1% of patients in OCTOPUS. After adjustment for age, sex, surgery type, randomisation, obesity, and hypertension, diabetes was associated with a 1.84-fold increased risk of POCD (OR 1.84; 95% CI 1.14, 2.97; p = 0.01). Obesity, BMI, hypertension, and baseline blood pressure were each not associated with POCD in fully adjusted models (all p > 0.05). Diabetes, but not obesity or hypertension, is associated with increased POCD risk. Consideration of diabetes status may be helpful for risk assessment of surgical patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Development of a high-volume aerosol collection system for the identification of air-borne micro-organisms.
A high-volume aerosol collector was developed to efficiently capture airborne bacteria in order to assess levels of diversity in the air. Particulate matter was collected on a device designed to filter 1.4 x 10(6) litres of air in a 24 h period on a 1-microm pore size polyester membrane. Methods were optimized for extraction of genomic DNA from the air filter concentrate. Preparation times of 90 s with 0.5-0. 05 mm diameter zirconia/silica beads yielded the highest concentration genomic DNA that was able to support PCR. A 24-h air sample was taken in Salt Lake City, Utah and the microbial composition was determined by the amplification and sequence analysis of 16S ribosomal DNA fragments. Sequence analysis revealed a large diversity in the type of microbial species present including clones matching the sequence of Clostridium botulinum. The primary components of the aerosol sample included many different spore-forming bacteria as well as more fragile members of the Proteobacteria division. The high-volume air collection and genomic DNA recovery system allows for the rapid detection of both cultivable as well as culture-resistant organisms in the environment. | {
"pile_set_name": "PubMed Abstracts"
} |
Low-dose estrogen is as effective as high-dose treatment in rats with postmenopausal hypertension.
: This study was conducted to test the hypothesis that 17β-estradiol therapy improves redox balance by decreasing reactive oxygen species production and increasing nitric oxide (NO) bioavailability, favoring Akt pathway activation and resulting in a better autonomic vascular control. Ovariectomized female Wistar rats were divided into 4 groups: (1) vehicle (VL) and animals treated with a pellet of 17β-estradiol for 21 days; (2) low dose (LE; 0.05 mg); (3) medium dose (ME; 0.2 mg); and (4) high dose (HE; 0.5 mg). Arterial pressure and its sympathetic nervous system modulation were evaluated by spectral analysis. Nitric oxide synthase and NADPH oxidase (Nox) activities, H2O2 concentration, redox status (GSH/GSSG), protein expression of Trx-1 and p-Akt/Akt were evaluated in the aorta, whereas NO metabolites were measured in the serum. Estrogen-treated groups showed a significant decrease in arterial pressure and sympathetic vascular drive. Redox status was significantly improved and NADPH oxidase and H2O2 were decreased in all estrogen-treated groups. Estrogen also induced an enhancement in NO metabolites, nitric oxide synthase activity, and Akt phosphorylation. This study demonstrated that estrogen treatment to ovariectomized rats induced cardioprotection, which was evidenced by reduced blood pressure variability and vascular sympathetic drive. These effects were associated with an improved redox balance and Akt activation, resulting in an enhanced NO bioavailability. | {
"pile_set_name": "PubMed Abstracts"
} |
Do Drinking and Smoking Go Together?
Heavy drinkers tend to be heavy smokers. Drinking appears to prompt smoking in real-life situations; whether smoking prompts drinking is uncertain. Alcohol-tobacco interactions are particularly important during attempts to achieve or maintain abstinence from either drug. Studies suggest that alcoholics who quit smoking are more likely to succeed in alcoholism treatment. However, data consistently demonstrate that alcohol consumption may precipitate smoking relapse. | {
"pile_set_name": "PubMed Abstracts"
} |
Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study.
Animal and in vitro data suggest that dyslipidemia plays an important role in the initiation and progression of chronic renal disease, but few prospective studies have been conducted in humans. We studied the relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or greater in 12,728 Atherosclerosis Risk in Communities (ARIC) participants with baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8 mg/dL in women. During a mean follow-up of 2.9 years, 191 persons had a rise in creatinine of 0.4 mg/dL or greater, yielding an incidence rate of 5.1 per 1000 person years. Individuals with higher triglycerides and lower high-density lipoprotein (HDL) and HDL-2 cholesterol at baseline were at increased risk for a rise in creatinine after adjustment for race, gender, baseline age, diabetes, serum creatinine, systolic blood pressure, and antihypertensive medication use (all P trends </=0.02). The adjusted relative risk for the highest versus lowest quartile of triglycerides was 1.65 (95% CI, 1.1, 2.5, P = 0.01) and for HDL was 0.47 (95% CI, 0.3, 0.8, P = 0.003). These associations were significant in participants with normal creatinine (defined as <1.4 mg/dL for men and <1.2 mg/dL for women), with diabetes, and without diabetes. The effect of high triglycerides was independent of plasma glucose, but was weaker and less consistent after further adjustment for fasting insulin in nondiabetics. High triglycerides and low HDL cholesterol, but not low-density lipoprotein cholesterol, predict an increased risk of renal dysfunction. The treatment of these lipid abnormalities may decrease the incidence of early renal disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Bilateral and simultaneous triceps avulsions in a patient with chronic renal failure receiving long-term peritoneal dialysis.
Simultaneous bilateral triceps tendon avulsions are extremely rare; only 4 cases have been reported in the international literature. This article describes a case of a 32-year-old woman with bilateral and simultaneous avulsions of the triceps tendons. She suffers from chronic renal failure and undergoes peritoneal dialysis every day. The patient presented with ecchymosis and swelling at the posterior aspect of both elbows. While climbing stairs a few hours earlier, she had fallen back on both outstretched arms, experienced moderate pain, and heard a sudden popping sound in her right elbow, followed by similar pain in the left elbow. On examination, she revealed intact extensor mechanism. Radiographs revealed a small osseous flake just proximal to the olecranon in both arms and the absence of associated fractures. During surgery, both triceps tendons appeared normal, other than being avulsed at their tendo-osseous junction. The patient obtained a successful result and full range of motion bilaterally within 3 months postoperatively. A high index of suspicion is needed and careful attention should be paid to elbow pain after minor trauma so that triceps injuries, especially in chronic kidney disease cases, are not missed. | {
"pile_set_name": "PubMed Abstracts"
} |
Identification, fermentation, and bioactivity against Xanthomonas oryzae of antimicrobial metabolites isolated from Phomopsis longicolla S1B4.
Bacterial blight, an important and potentially destructive bacterial disease in rice, is caused by Xanthomonas oryzae. Recently, this organism has developed resistance to available antibiotics, prompting scientists to find a suitable alternative. This study focused on secondary metabolites of Phomopsis longicolla to target X. oryzae. Five bioactive compounds were isolated by activity-guided fractionation from ethyl acetate extracts of mycelia and were identified by LC/MS and NMR spectroscopy as dicerandrol A, dicerandrol B, dicerandrol C, deacetylphomoxanthone B, and fusaristatin A. This is the first time fusaristatin A has been isolated from Phomopsis sp. Deacetylphomoxanthone B showed a higher antibacterial effect against X. oryzae KACC 10331 than the positive control (2,4-diacetyphloroglucinol). Dicerandrol A also showed high antimicrobial activity against Grampositive bacteria (Staphylococcus aureus, Bacillus subtilis) and yeast (Candida albicans). In addition, high production yields of these compounds were obtained at the stationary and death phases. | {
"pile_set_name": "PubMed Abstracts"
} |
p-Aminohippurate transport in basal-lateral membrane vesicles from rabbit renal cortex: stimulation by pH and sodium gradients.
p-Aminohippuric acid (PAH) uptake was studied in basal-lateral membrane vesicles prepared from rabbit renal cortex. An outwardly directed hydroxyl gradient (pHo = 6.0, pHi = 7.6) stimulated PAH uptake slightly over that when the internal and external pH values were equal at 7.6. A 100 mM sodium gluconate gradient directed into the basal-lateral membrane vesicles increased PAH uptake about 2-fold over that when N-methyl-D-glucamine or potassium gluconate gradients were present. When hydroxyl and sodium gradients were simultaneously imposed (pHo = 6.0, pHi = 7.6 and 100 mM sodium gluconate extravesicularly) PAH uptake was stimulated greater than with the pH or Na+ gradient alone. In fact, an 'overshoot' was observed. Countertransport experiments showed that either intravesicular PAH or intravesicular PAH and Na+ could stimulate 3H-PAH uptake. Probenecid, an inhibitor of organic anion transport, inhibited both the hydroxyl-stimulated and Na+ gradient-stimulated PAH uptake but the greatest inhibition by probenecid was seen when the hydroxyl and sodium gradients were both present. Thus, it is proposed that the driving force for PAH accumulation across the basal-lateral membrane of the proximal tubule is a transport system which moves Na+ and PAH into the cell for an hydroxyl ion leaving the cell, i.e. a sodium-dependent anion-anion exchange system. | {
"pile_set_name": "PubMed Abstracts"
} |
Evaluation of the obesity surgery mortality risk score for the prediction of postoperative complications after primary and revisional laparoscopic Roux-en-Y gastric bypass.
The Obesity Surgery Mortality Risk Score (OS-MRS) is a validated instrument for mortality risk prediction in patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) procedures classifying patients into low risk (class A), intermediate risk (class B), and high risk (class C). The primary aim of this study was to evaluate the accuracy of the OS-MRS in predicting postoperative complications after LRYGB. Secondarily, the postoperative complication rate between primary and revisional LRYGB was systematically analyzed. The Obesity Center Amsterdam, located in a large teaching hospital, in Amsterdam, The Netherlands. The OS-MRS was applied to a consecutive database of patients who underwent LRYGB from November 2007 onwards. Postoperative complications were scored according to the Clavien-Dindo classification. Revisional LRYGB was separately analyzed. LRYGB was performed in 1667 patients either as a primary (81.5%) or revisional (18.5%) procedure. The majority (n = 1371, 82.2%) were female, mean age 44.6 (standard deviation 14.4) years and mean body mass index 44.2 (6.5) kg/m2. Nine hundred and four (54.2%) were OS-MRS class A, 642 class B (38.5%), and 121 (7.3%) class C. Complications occurred in 143 (10.5%) and 44 (14.2%) patients after primary and revisional surgery, respectively. In both primary and revisional LRYGB, there was no association between complications and the OS-MRS classification. Subanalysis comparing primary with revisional LRYGB found a significant association between revisional surgery and the development of severe complications (Clavien-Dindo≥3) (P = .003) and mortality (P = .017). The OS-MRS was not an accurate predictor for postoperative complications in patients who underwent primary or revisional LRYGB. As in other studies, revisional surgery is an independent risk factor for the development of severe complications. | {
"pile_set_name": "PubMed Abstracts"
} |
Posterior weighted reinforcement learning with state uncertainty.
Reinforcement learning models generally assume that a stimulus is presented that allows a learner to unambiguously identify the state of nature, and the reward received is drawn from a distribution that depends on that state. However, in any natural environment, the stimulus is noisy. When there is state uncertainty, it is no longer immediately obvious how to perform reinforcement learning, since the observed reward cannot be unambiguously allocated to a state of the environment. This letter addresses the problem of incorporating state uncertainty in reinforcement learning models. We show that simply ignoring the uncertainty and allocating the reward to the most likely state of the environment results in incorrect value estimates. Furthermore, using only the information that is available before observing the reward also results in incorrect estimates. We therefore introduce a new technique, posterior weighted reinforcement learning, in which the estimates of state probabilities are updated according to the observed rewards (e.g., if a learner observes a reward usually associated with a particular state, this state becomes more likely). We show analytically that this modified algorithm can converge to correct reward estimates and confirm this with numerical experiments. The algorithm is shown to be a variant of the expectation-maximization algorithm, allowing rigorous convergence analyses to be carried out. A possible neural implementation of the algorithm in the cortico-basal-ganglia-thalamic network is presented, and experimental predictions of our model are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
A conformational analysis of mouse Nalp3 domain structures by molecular dynamics simulations, and binding site analysis.
Scrutinizing various nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) genes in higher eukaryotes is very important for understanding the intriguing mechanism of the host defense against pathogens. The nucleotide-binding domain (NACHT), leucine-rich repeat (LRR), and pyrin domains (PYD)-containing protein 3 (Nalp3), is an intracellular innate immune receptor and is associated with several immune system related disorders. Despite Nalp3's protective role during a pathogenic invasion, the molecular features and structural organization of this crucial protein is poorly understood. Using comparative modeling and molecular dynamics simulations, we have studied the structural architecture of Nalp3 domains, and characterized the dynamic and energetic parameters of adenosine triphosphate (ATP) binding in NACHT, and pathogen-derived ligands muramyl dipeptide (MDP) and imidazoquinoline with LRR domains. The results suggested that walker A, B and extended walker B motifs were the key ATP binding regions in NACHT that mediate self-oligomerization. The analysis of the binding sites of MDP and imidazoquinoline revealed LRR 7-9 to be the most energetically favored site for imidazoquinoline interaction. However, the binding free energy calculations using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method indicated that MDP is incompatible for activating the Nalp3 molecule in its monomeric form, and suggest its complex interaction with NOD2 or other NLRs accounts for MDP recognition. The high binding affinity of ATP with NACHT was correlated to the experimental data for human NLRs. Our binding site prediction for imidazoquinoline in LRR warrants further investigation via in vivo models. This is the first study that provides ligand recognition in mouse Nalp3 and its spatial structural arrangements. | {
"pile_set_name": "PubMed Abstracts"
} |
Thoracoscopy: a collaborative surgical approach.
Perioperative nurses, surgeons, anesthesiologists, certified registered nurse anesthetists, and pharmacists are meeting the challenge of decreasing thoracic surgical patients' length of hospital stay with thoracoscopy. This innovative alternative to traditional thoracotomy procedures has been achieved through an attentive team approach using the fundamental perioperative skills of assessment, positioning, safety, and sharing of knowledge. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of irradiation with fast neutrons or X-rays on the incidence of metastasis of transplanted B16 melanoma in mice.
The effects of X-rays and fast neutrons on the incidence of metastasis of B16 melanoma were investigated. Tumors were irradiated with the iso-effect dose (380 rad of 2 MeV fast neutrons, and 1900 rad of 200 kV X-rays) for regression and regrowth of the tumor, and then were excised 3 days after irradiation. Metastasis was examined macroscopically and microscopically in all organs and tissues of mice when death occurred or after sacrifice of surviving mice at 130 days after tumor inoculation. Metastasis was found in 16 to 22% of tumor-bearing mice irrespective of whether or not the tumor had been irradiated before excision. Almost all the mice with metastasis developed pulmonary metastasis accompanied by lymphogenous spread to the thoracic lymph node. The overall incidence of metastasis in the X- or fast neutron-irradiated mice was slightly but not significantly higher than that in the control mice. Irradiation significantly enhanced the incidence of metastasis when the tumor volume was smaller than 200 mm3, but not when the tumor volume was larger than 200 mm3. The incidence of metastasis was significantly enhanced in mice with tumors invading the muscle. The metastasis-enhancing effect of irradiation was noticeably greater with X-irradiation than with fast neutron irradiation in mice with localized tumors of B16 melanoma, whereas in mice with invasive tumors the effects were similar. | {
"pile_set_name": "PubMed Abstracts"
} |
Immunologic contact urticaria.
The wheal and flare reaction from direct contact with a chemical or protein agent is known as contact urticaria. Contact urticaria can be either nonimmunologic (no sensitization required) or immunologic (sensitization required). Immunologic contact urticaria often gives a more aggravated response and has the potential to spread from the local vicinity. Skin testing in immunologic contact urticaria gives a quicker response compared with skin testing in nonimmunologic contact urticaria. There are a wide variety of agents that can cause immunologic contact urticaria, and they can be either low-molecular-weight chemicals (haptens) or proteins. | {
"pile_set_name": "PubMed Abstracts"
} |
[Role of radiology in the diagnosis of aortic dissection].
Aortic dissection requires a prompt diagnosis and must be treated without delay in order to reduce the mortality rate. Whereas aortic dissection involving the ascending aorta (type A) requires immediate surgery, aortic dissection involving the descending aorta (type B) will usually be treated conservatively. This review article reevaluates the respective efficiency of conventional and modern radiological means offered in a well equipped university hospital. | {
"pile_set_name": "PubMed Abstracts"
} |
Critical reflections on school-based occupational therapy.
This article describes the process of facilitating change to practice that is more client-centered and occupation-based in a diverse suburban public school district in the USA from 2001 to 2006. The author sets the context, describes the process that included the use of the School AMPS, and considers factors that facilitated and constrained change. | {
"pile_set_name": "PubMed Abstracts"
} |
The localization of brain sites of anxiogenic-like effects of urocortin-2.
The influence of intracerebroventricullary-administered urocortin-2, a selective corticotropin-releasing factor receptor 2 (CRF(2)) agonist, on rat anxiety-like behaviour, the expression of c-Fos and CRF, and plasma corticosterone levels was examined in the present study. When applied to animals exposed to the conditioned fear-induced context, urocortin-2 enhanced a conditioned freezing fear response. Urocortin-2 also significantly decreased rat exploratory activity in the open field test. Exogenous urocortin-2 increased the conditioned fear-induced expression of c-Fos in the central amygdala (CeA), and parvocellular neurons of the paraventricular hypothalamic nucleus (pPVN), and revealed the effect of conditioned fear in the medial amygdala (MeA). In the fear-conditioned animals, immunocytochemistry showed an increase in the density of CRF-related immunoreactive complexes in the lateral septum (LS), 35min after urocortin-2 administration and 10min after the conditioned fear test, compared with saline-pretreated fear-conditioned animals. These data suggest a role of urocortin-2 in the behavioural and immunocytochemical responses to stress, in which it strengthens the measures of anxiety-like responses. | {
"pile_set_name": "PubMed Abstracts"
} |
Down-regulation of keratin 14 gene expression after v-Ha-ras transfection of human papillomavirus-immortalized human cervical epithelial cells.
Keratin expression in human cervical squamous cell carcinoma (SCC) lines differed significantly from both normal and human papillomavirus (HPV) immortalized exocervical cells. Keratin 14 (K14) expression, determined by protein synthesis and mRNA levels, was dramatically down-regulated in the cervical SCC lines while keratin 5 (K5) expression was not. K14 expression was similarly down-regulated in an HPV-16 immortalized cervical cell line after tumorigenic transformation with recombinant v-Ha-ras DNA. Cultures derived from nude mouse tumor explants also exhibited an altered keratin profile and the levels of K14 protein synthesis, as well as K14 mRNA, were not detectable. In both cases K5 protein synthesis was not significantly down-regulated. In addition, neoplastic cervical SCC lines exhibited up-regulation of keratins 7, 8, 13, and 19, combined with slight down-regulation of keratins 6 and 16. Epidermal keratinocytes responded in a different manner to exocervical cells. Transfection of human papillomavirus-immortalized epidermal keratinocytes with the BglII N fragment of herpes simplex virus 2 produced a neoplastic cell line, but K5 and K14 expression remained unchanged. Thus, neoplastic transformation of human exocervical cells, both in vivo (spontaneous cervical SCC) and in vitro (HPV-16- and v-Ha-ras-induced cervical SCC), is accompanied by characteristic changes in keratin expression. The specific down-regulation of K14 in these tumorigenic cervical cells, in the absence of significant changes in the expression of K5, implies that the normal coordinate regulation of K5 and K14 gene expression has been uncoupled. | {
"pile_set_name": "PubMed Abstracts"
} |
Parents' experiences of participation in physical activities for children with cerebral palsy - protecting and pushing towards independence.
To explore how parents of children with cerebral palsy (CP) experience their child's participation in physical activities and to identify facilitators and barriers for being physically active and reducing sedentary behaviour. Twenty-five parents of sixteen children, aged 8-11 years old with CP, with varying gross motor, cognitive and communicative functions and with different cultural backgrounds, participated in focus group or individual interviews. Content analysis was used for analysis. Five subcategories addressing children's participation in physical activity were found: "Belonging and taking space in the family", "Important persons facilitating and hindering", "Friends important but hard to get", "Good for the body but challenging" and "Availability and opting out possibilities". The subcategories built the main category "Protecting and pushing towards independence", expressing the challenges parents experienced when their child wanted to be physically active. Parents desire competent persons to be available for support in participation in physical activities. They want support in finding friends for their child to be physically active with. Family culture and attitudes affect their child's motivation for being physically active and should be taken into account when designing interventions for increased participation in physical activities and for reduced sedentary behaviour in children with disabilities. Implications for Rehabilitation Friends and competent adults facilitate participation in physical activities and reduce sedentary behaviour. Information on accessible and tailored physical activities is an important facilitator for participation in physical activities. Service planning and design of interventions may be facilitated by taking the individual family culture into account. | {
"pile_set_name": "PubMed Abstracts"
} |
Specific IgE antibody response to human insulin in diabetic subjects.
Treatment with heterologous insulin preparations induce insulin antibody formation in most of the patients. A hundred of diabetic individuals in treatment with human insulin (HI) for at least 6 months at the time of the study and without any clinical immunological reaction, were selected in order to study the development of specific IgE antibodies against HI by in vivo and in vitro methods. Serologic specific IgE antibodies to HI were measured by RAST (Pharmacia) and 5 RAST-positive subjects were found. The specificity of these results were confirmed in 4 of the 5 subjects by RAST-inhibition. Thus, the prevalence of specific serologic IgE to HI in our study was 4% (1.1%-9.9%, p < 0.05). Only two of the RAST-positive subjects had cutaneous reactivity to HI by intradermal technique and one of the RAST-negative subjects presented also insulin skin reactivity. HI skin reactivity was found in 3% (0.6%-8.5%, p < 0.05) of the 100 diabetic subjects. These results differ from others obtained with heterologous insulins. | {
"pile_set_name": "PubMed Abstracts"
} |
Endotoxic shock and its effects on hepatobiliary scanning in dogs.
Hepatobiliary scans were obtained with Tc-99m-disofenin in 15 dogs. Of these, 5 served as controls, 5 were infused with E. coli endotoxin for 4 hours (endotoxic shock group), and 5 were bled to a mean pressure similar to that of the endotoxic shock group (hemorrhagic shock group). Scans of the controls and hemorrhagic shock group were identical. Scans of the endotoxic shock group were markedly abnormal, with a prolonged hepatic phase and little excretion of isotope into the biliary tract, a pattern characteristic of mechanical obstruction of the common bile duct. These results should alert the clinician to the potential danger of abnormal hepatobiliary scans in the septic patient. | {
"pile_set_name": "PubMed Abstracts"
} |
The σ-aromatic clusters [Zn₃]⁺ and [Zn₂Cu]: embryonic brass.
The triangular clusters [Zn3Cp*3](+) and [Zn2CuCp*3] were obtained by addition of the in situ generated, electrophilic, and isolobal species [ZnCp*](+) and [CuCp*] to Carmona's compound, [Cp*Zn-ZnCp*], without splitting the ZnZn bond. The choice of non-coordinating fluoroaromatic solvents was crucial. The bonding situations of the all-hydrocarbon-ligand-protected clusters were investigated by quantum chemical calculations revealing a high degree of σ-aromaticity similar to the triatomic hydrogen ion [H3](+). The new species serve as molecular building units of Cu(n)Zn(m) nanobrass clusters as indicated by LIFDI mass spectrometry. | {
"pile_set_name": "PubMed Abstracts"
} |
Three-dimensional video-assisted thoracoscopic pericardiectomy.
Video-assisted thoracic surgery has proven to be safe and effective for the diagnosis and management of pericardial disease. Three-dimensional (3-D) video imaging technology has been developed to allow the laparoscopic surgeon more precision and efficiency in advanced laparoscopic cases. This case report describes the marriage of 3-D video imaging and thoracoscopy that allowed performance of a technically difficult pericardiectomy without incident. Our aim is to describe the use of state-of-the-art 3-D video imaging to allow success in difficult cases. | {
"pile_set_name": "PubMed Abstracts"
} |
Docking and three-dimensional quantitative structure-activity relationship (3D QSAR) analyses of nonsteroidal progesterone receptor ligands.
We report a docking and comparative molecular similarity indices analysis (CoMSIA) study of progesterone receptor (PR) ligands with an emphasis on nonsteroids including tanaproget. The ligand alignment generation, a critical part of model building, comprised two stages. First, thorough conformational sampling of docking poses within the PR binding pocket was made with the program GOLD. Second, a strategy to select representative poses for CoMSIA was developed utilizing the FlexX scoring function. After manual replacement of five poses where this approach had problems, a significant correlation (r(2) = 0.878) between the experimental affinities and electrostatic, hydrophobic, and hydrogen bond donor properties of the aligned ligands was found. Extensive model validation was made using random-group cross-validations, external test set predictions (r(pred)(2) = 0.833), and consistency check between the CoMSIA model and the PR binding site structure. Robustness, predictive ability, and automated alignment generation make the model a potential tool for virtual screening. | {
"pile_set_name": "PubMed Abstracts"
} |
Cultivation of methanotrophic bacteria in opposing gradients of methane and oxygen.
In sediments, methane-oxidizing bacteria live in opposing gradients of methane and oxygen. In such a gradient system, the fluxes of methane and oxygen are controlled by diffusion and consumption rates, and the rate-limiting substrate is maintained at a minimum concentration at the layer of consumption. Opposing gradients of methane and oxygen were mimicked in a specific cultivation set-up in which growth of methanotrophic bacteria occurred as a sharp band at either c. 5 or 20 mm below the air-exposed end. Two new strains of methanotrophic bacteria were isolated with this system. One isolate, strain LC 1, belonged to the Methylomonas genus (type I methantroph) and contained soluble methane mono-oxygenase. Another isolate, strain LC 2, was related to the Methylobacter group (type I methantroph), as determined by 16S rRNA gene and pmoA sequence similarities. However, the partial pmoA sequence was only 86% related to cultured Methylobacter species. This strain accumulated significant amounts of formaldehyde in conventional cultivation with methane and oxygen, which may explain why it is preferentially enriched in a gradient cultivation system. | {
"pile_set_name": "PubMed Abstracts"
} |
Estimation of disease severity in the NHS cervical screening programme. Part II: quantitative methods of estimating disease severity and progression potential.
This is the second of a two-part paper exploring the use of a more quantitative approach to both cytology and histology disease severity measurements. In Part I the problem of artificial cut-off points was discussed and a semi-quantitative solution to the problem proposed. In Part II quantitative methods are proposed that are used to predict the estimated progression probability (EPP) to invasive cancer. Based on models derived from published data the grade number (GN) is related to the EPP to invasive cancer over the next 10 years for both cytology (CEPP) and histology (HEPP) using a look-up table. CEPP and HEPP are then adjusted by other factors such as age, persistence, HPV result, number of cells and lesion size to obtain the adjusted CEPP and HEPP (ACEPP and (AHEPP). The two factors can be combined to produce an adjusted weighted estimated progression potential using the formula AWEPP √((ACEPP + AHEPP)/2) × AHEPP) using a two to one bias in favour of the histology. As an example of the methodology consider a slide estimated as showing a 60% probability of moderate dyskaryosis (HSIL favouring CIN2) and 40% probability of mild dyskaryosis (LSIL favouring CIN1). The GN number would be 1.6 (as described in Part I) and the EPP over the next 10 years 0.78%. For a woman aged 52 years (correction factor ×2.0) with a second mildly dyskaryotic smear (correction factor ×1.25) and >50 dyskaryotic cells (correction factor 1.5) the ACEPP would be 0.78 × 2.00 × 1.25 × 1.5 = 2.9%. If the HEPP on histology was 50:50 between CIN1 and CIN2, the AHEPP can be calculated as 1.4%. The AWEPP would be √((2.9 + 1.4)/2 × 1.4) = 1.7%. The final estimate of disease progression potential based on both cytology and histology is 1.7% over 10 years. These quantitative approaches based on adjusted and weighted EPP provide a framework suitable for research, audit and comparison between screening centres, and for tailoring criteria for colposcopy referral and treatment. Further research is required to improve the estimates given in the paper. | {
"pile_set_name": "PubMed Abstracts"
} |
Functional platform for controlled subcellular distribution of carbon nanotubes.
As nanoparticles can cross different cellular barriers and access different tissues, control of their uptake and cellular fate presents a functional approach that will be broadly applicable to nanoscale technologies in cell biology. Here we show that the trafficking of single-walled carbon nanotubes (SWCNTs) through various subcellular membranes of the plant cell is facilitated or inhibited by attaching a suitable functional tag and controlling medium components. This enables a unique control over the uptake and the subcellular distribution of SWCNTs and provides a key strategy to promote their cellular elimination to minimize toxicity. Our results also demonstrate that SWCNTs are involved in a carrier-mediated transport (CMT) inside cells; this is a phenomenon that scientists could use to obtain novel molecular insights into CMT, with the potential translation to advances in subcellular nanobiology. | {
"pile_set_name": "PubMed Abstracts"
} |
Delineating a Ca2+ binding pocket within the venus flytrap module of the human calcium-sensing receptor.
The Ca(2+)-sensing receptor (CaSR) belongs to the class III G-protein-coupled receptors (GPCRs), which include receptors for pheromones, amino acids, sweeteners, and the neurotransmitters glutamate and gamma-aminobutyric acid (GABA). These receptors are characterized by a long extracellular amino-terminal domain called a Venus flytrap module (VFTM) containing the ligand binding pocket. To elucidate the molecular determinants implicated in Ca(2+) recognition by the CaSR VFTM, we developed a homology model of the human CaSR VFTM from the x-ray structure of the metabotropic glutamate receptor type 1 (mGluR1), and a phylogenetic analysis of 14 class III GPCR VFTMs. We identified critical amino acids delineating a Ca(2+) binding pocket predicted to be adjacent to, but distinct from, a cavity reminiscent of the binding site described for amino acids in mGluRs, GABA-B receptor, and GPRC6a. Most interestingly, these Ca(2+)-contacting residues are well conserved within class III GPCR VFTMs. Our model was validated by mutational and functional analysis, including the characterization of activating and inactivating mutations affecting a single amino acid, Glu-297, located within the proposed Ca(2+) binding pocket of the CaSR and associated with autosomal dominant hypocalcemia and familial hypocalciuric hypercalcemia, respectively, genetic diseases characterized by perturbations in Ca(2+) homeostasis. Altogether, these data define a Ca(2+) binding pocket within the CaSR VFTM that may be conserved in several other class III GPCRs, thereby providing a molecular basis for extracellular Ca(2+) sensing by these receptors. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effect of grazing on reproduction in Leymus chinensis population].
The experiment on the effect of grazing on the asexual and sexual reproduction and biomass allocation in Leymus chinensis population was conducted in Songnen grassland. The results show that animal grazing reduced both asexual and sexual reproductive channels. With the increase of grazing intensity, the densities of asexual shoots and rhizome tillers, seed biomass, numbers of seeds per inflorescence and sexual shoot ratio decreased significantly, especially after heavy grazing. The rates of biomass allocation to rhizome increased significantly with increasing grazing intensity, while the rates of biomass allocation to assimilation, unassimilation organs and seed production decreased remarkably. In the haviest grazing stage, there were almost no sexual shoots. | {
"pile_set_name": "PubMed Abstracts"
} |
[Epidemiological surveillance of influenza in western Sicily in 1976-1977].
Two strains of influenza virus A/H3N2 antigenically similar to A/Victoria/3/75 have been isolated in Palermo in February 1977; a peak of extramortality has been observed in the same month, and a rise of HAI antibodies for A/H3N2 viruses in human serum samples, taken from apparently healthy subjects living Palermo, has been demonstrated between October 1976 and February 1977. Similar rise of antibody titers has also taken place in serum samples from two communities in Western Sicily (Favara, 30,000 inhabitants, Favignana, 3,000 inhabitants). Serum samples obtained in June 1977 showed a slight fall of antibody level in Palermo and in Favignana, whereas in Favara a further rise, in comparison to February, is consistent with the hypothesis of a delayed circulation of virus in that community. Reduction of HAI titers for H3N2 viruses was even more pronounced in October 1977 in all groups of serum samples tested. The importance of local surveillance of influenza and the assessment of herd immunity level is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Optimal cut-off for hourly lactate reduction in ICU-treated patients with septic shock.
A decrease in lactate concentration over time during septic shock is associated with favourable outcomes. However, if this applies to hourly intervals during the initial time period in the ICU is unknown. The aim of this study was to investigate whether there is an early hourly reduction rate of lactate that is related to clinical outcome in septic shock patients treated in the ICU. A cohort of adult septic shock patients admitted to the ICU with an initial lactate level >2 mmol/L and receiving vasopressor was retrospectively analysed. Mean hourly reduction rate of lactate (ΔLact/h) was calculated individually from all lactate concentrations measured from inclusion until normalization of lactate (≤1.5 mmol/L) within 24 hours. The mortality at 30 days following ICU admission was evaluated. Among 1405 ICU admissions during 2 years, 104 patients were eligible. Mortality rate at 30 days was 34%. The optimal cut-off values of baseline lactate and ΔLact/h for 30-day mortality were 4 mmol/L and 2.5%/h. When stratifying the patients by these cut-points, those with baseline lactate > 4 mmol/L and ΔLact/h < 2.5%/h had lowest probability of survival (27%). Multivariable logistic regression showed that ΔLact/h <2.5%/h, baseline lactate >4 mmol/L and high Simplified Acute Physiology Score III were independent risk factors of 30-day mortality. In this retrospective pilot cohort, a mean reduction rate of lactate <2.5%/h within the first 24 hours of ICU stay was associated with an increased risk of 30-day mortality in septic shock patients. | {
"pile_set_name": "PubMed Abstracts"
} |
[Changes in the induction and repair of double-stranded DNA breaks in pro- and eukaryote cells. I. Use of a Zimm elastoviscosimeter to study induction of double-stranded DNA breaks in gamma-irradiated Escherichia coli cells].
The technique of elastoviscosimetry allows to study the induction of double-strand breaks in DNA of E. coli at low doses (on the order of D37). The dose dependence of retardation time to shows a characteristic maximum. It is shown that the ascending part of the curve is due to the phenomenon of relaxation of supercoiled DNA in the bacterial nucleoid. Relaxation is effected by different gamma-induced damages in DNA which are not double-strand breaks. The position of the maximum yields the average dose for the formation of the first double-strand break, which transforms the circular DNA into a linear chain. The descending part of the dose curve is explained by accumulation of additional double-strand breaks. The gamma-irradiation and lysis of cells was performed in different media. It was found that only in the case when the action of nucleases was substantially (but not completely) inhibited, the position of the maximum of the dose dependent of retardation time coincides satisfactorily with the value of D37 (14.5 +/- 2.3 and 12.5 +/- 3 krad correspondingly). If the medium does not contain inhibitors of nucleases then the position of the maximum corresponds to a 4.2 times lower dose of gamma-rays. This shows that double-strand breaks in gamma-irradiated DNA are generated mainly by enzymes participating in repair processes and that the first double-strand breaks seems to be the true reason of lethality because of inability to be repaired. | {
"pile_set_name": "PubMed Abstracts"
} |
Endocrine cancer predisposition syndromes: hereditary paraganglioma, multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2, and hereditary thyroid cancer.
The hereditary paraganglioma, MEN1, MEN2, and hereditary thyroid cancer syndromes are clinically discernable and genetically distinct. The first 3 syndromes have been well characterized in the past 10 to 15 years. Recognizing these 3 syndromes and using a multidisciplinary team approach creates valuable opportunities for early diagnosis, reduction of morbidity and mortality, and avoidance of surgical misadventures. Hereditary paraganglioma has parent-of-origin effects and gene-environment interactions that indicate its evolution, and the syndrome sheds light on the role of mitochondria and energy metabolism in cancer. This article delineates the clinical presentation and practical management issues and summarizes the history, gene discovery, and molecular insights for each syndrome. | {
"pile_set_name": "PubMed Abstracts"
} |
The medical and veterinary role of Ornithodoros erraticus complex ticks (Acari: Ixodida) on the Iberian Peninsula.
Argasid ticks of the Ornithodoros erraticus complex are associated with traditional pig-farming practices on the Iberian Peninsula and are also found elsewhere in North Africa, West Africa, and western Asia. The ticks associated with pig farming on the Iberian Peninsula are the only biological vectors of African swine fever virus (ASFV) known to occur in Europe, and their ecology makes them an extremely effective reservoir of both ASFV and the Borrelia species which cause tick-borne relapsing fever (TBRF) in humans. The recent reappearance of ASFV in the European Union, coupled with evidence that Portuguese tick populations continue to harbor Borrelia despite a lack of confirmed human infections, suggest that these populations merit closer attention. In Portugal, a series of surveys over the last twenty-five years indicates that the number of farm sites with tick infestations has declined and suggest that populations are sensitive to changes in farm management, particularly the use of modern pig housing. Various technologies have been suggested for the control of farm-associated Ornithodoros ticks and related species but, in our opinion, farm management changes are still the most effective strategy for population control. Furthermore, we suggest that this species could probably be eradicated from Iberian pig farms. | {
"pile_set_name": "PubMed Abstracts"
} |
[Intra-abdominal soft tissue tumors. What needs to be known to reach the diagnosis with the help of immunohistochemistry, FISH and molecular biology].
Connective tissue tumors located inside the abdomen are a rare heterogeneous group of tumors, except for gastro-intestinal stromal tumors. They may be benign, malignant, or intermediate in terms of biologic potential. Pathologists have to remember the list of all the lesions possibly involved, with their immunohistochemical characteristics, and to know which molecular analyses are needed, with which expected results, and by which team they can be performed. The main tumor types are discussed with diagnostic tools and treatment consequences. | {
"pile_set_name": "PubMed Abstracts"
} |
Fujinon intelligent color enhancement for the diagnosis of early esophageal squamous cell carcinoma and precancerous lesion.
Esophageal squamous cell carcinoma is a common malignant tumor in recent years, and the key for improving the survival rate is early diagnosis and treatment. Computed virtual chromoendoscopy with the Fujinon intelligent color enhancement (FICE) system was reported to improve visualization of neoplastic and non-neoplastic lesions in gastroscopy and colonoscopy. The purpose of this study was to evaluate the value of FICE in the diagnosis of early esophageal squamous cell carcinoma and precancerous lesions. Two hundred fifty-seven patients with suspicious lesions of the esophagus were examined successively by FICE, magnifying FICE, Lugol chromoendoscopy, and magnifying Lugol chromoendoscopy in the hospital. The lesions and the intrapapillary capillary loop (IPCL, microvessels at the surface of esophageal carcinoma) were observed and compared with the pathologic diagnosis that was regarded as the golden standard. The positive rates of early esophageal squamous cell carcinoma were 92.6% and 88.9% as examined by FICE and Lugol chromoendoscopy (p>0.05), and 96.3% and 92.6% as examined by magnifying FICE and magnifying Lugol chromoendoscopy (p>0.05), respectively. The magnifying FICE could observe the IPCL of the esophagus clearly. Early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia were mainly type IV and type V. Low-grade intraepithelial neoplasia and esophagitis were type II and type III, and normal esophagus was type I; however, the observation of the IPCL by magnifying Lugol chromoendoscopy was not clear. Fujinon intelligent color enhancement and magnifying FICE are complements to Lugol chromoendoscopy and magnifying Lugol chromoendoscopy in the diagnosis of early esophageal lesions. | {
"pile_set_name": "PubMed Abstracts"
} |
Detection of protein three-dimensional side-chain patterns: new examples of convergent evolution.
Detection of recurring three-dimensional side-chain patterns is a potential means of inferring protein function. This paper presents a new method for detecting such patterns and discusses various implications. The method allows detection of side-chain patterns without any prior knowledge of function, requiring only protein structure data and associated multiple sequence alignments. A recursive, depth-first search algorithm finds all possible groups of identical amino acids common to two protein structures independent of sequence order. The search is highly constrained by distance constraints, and by ignoring amino acids unlikely to be involved in protein function. A weighted root-mean-square deviation (RMSD) between equivalenced groups of amino acids is used as a measure of similarity. The statistical significance of any RMSD is assigned by reference to a distribution fitted to simulated data. Searches with the Ser/His/Asp catalytic triad, a His/His porphyrin binding pattern, and the zinc-finger Cys/Cys/His/His pattern are performed to test the method on known examples. An all-against-all comparison of representatives from the structural classification of proteins (SCOP) is performed, revealing several new examples of evolutionary convergence to common patterns of side-chains within different tertiary folds and in different orders along the sequence. These include a di-zinc binding Asp/Asp/His/His/Ser pattern common to alkaline phosphatase/bacterial aminopeptidase, and an Asp/Glu/His/His/Asn/Asn pattern common to the active sites of DNase I and endocellulase E1. Implications for protein evolution, function prediction and the rational design of functional regulators are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Generation of cancer vaccine immunogens derived from major histocompatibility complex (MHC) class I molecules using variable epitope libraries.
Although various immune checkpoint inhibitors (ICIs), used for the treatment of advanced cancer, showed remarkably durable tumor regression in a subset of patients, there are important limitations in a large group of non-responders, and the generation of novel immunogens capable of inducing protective cellular immune responses is a priority in cancer immunotherapy field. During the last decades, several types of vaccine immunogens have been used in numerous preclinical studies and clinical trials. However, although immunity to tumor Ags can be elicited by most vaccines tested, their clinical efficacy remains modest. Recently, we have developed an innovative vaccine concept, called Variable Epitope Libraries (VELs), with the purpose to exploit the high antigenic variability of many important pathogens and tumor cells as starting points for the construction of a new class of vaccine immunogens capable of inducing the largest possible repertoire of both B and T cells. In the present study, we decided to generate VEL immunogens derived from both classical and non-classical major histocompatibility complex (MHC) class I molecules. The MHC molecules, responsible for antigen presentation and subsequent activation of T lymphocytes, undergo multiple modifications that directly affect their proper function, resulting in immune escape of tumor cells. Two large VELs derived from multi-epitope region of H2-Kd and Qa-2 sequences (46 and 34 amino acids long, respectively), along with their wild type counterparts have been generated as synthetic peptides and tested in an aggressive 4T1 mouse model of breast cancer. Significant inhibition of tumor growth and the reduction of metastatic lesions in the lungs of immunized mice were observed. This study demonstrated for the first time the successful application of VELs carrying combinatorial libraries of epitope variants derived from MHC class I molecules as novel vaccine immunogens. | {
"pile_set_name": "PubMed Abstracts"
} |
Down-regulation in vivo of PGE receptors and adenylate cyclase stimulation.
Down-regulation in vivo of liver plasma membrane receptors for prostaglandin E (PGE) was investigated in Sprague-Dawley rats using the 16,16-dimethyl analogue of PGE2, This analogue was used for subcutaneous injections because it escapes the rapid pulmonic degradation characteristic of PGE and was recognized well by liver plasma membrane receptors. Following treatment with the analogue, the concentration of PGE receptors was significantly decreased (-37%, P less than 0.001), but the binding affinity was not altered. There was no evidence for carry-through of the analogue into the isolated plasma membrane preparation. It was also demonstrated that GTP decreased the binding affinity between PGE and its receptor. Down-regulation of receptor concentration was associated with a significant decrease (P less than 0.001) in PGE1-stimulated plasma membrane adenylate cyclase activity. These data provide the novel demonstration that rat liver plasma membrane receptor for PGE can be down-regulated in vivo and that this causes a corresponding decrease in PGE-induced plasma membrane adenylate cyclase activity. | {
"pile_set_name": "PubMed Abstracts"
} |
Two-week eradication regimen for metronidazole-resistant Helicobacter pylori.
At present there is no generally accepted treatment regimen for eradicating metronidazole-resistant Helicobacter pylori. This study determines the eradication rate after treatment with 40 mg omeprazole o.m. and 500 mg amoxycillin q.d.s. for 14 days, with 120 mg tripotassium dicitrato bismuthate q.d.s. for the first week (Days 1-7) and 750 mg ciprofloxacin b.d. for the second week (Days 8-14). Thirty patients (16 male, mean age 45 years, range 16-80 years) with duodenal ulcers (n = 18) or non-ulcer dyspepsia (n = 2) and metronidazole-resistant H. pylori detected by histology, culture, in vitro sensitivity tests and a positive 13C-urea breath test entered the study. Follow-up was by 13C-urea breath test at the end of treatment and at 1, 3, 6, and 12 months. Eradication was defined as a negative 13C-urea breath test at least 1 month after finishing treatment. H. pylori was successfully eradicated in 21/30 (71%) patients (median follow-up 10.2 months, range 4-12 months). A pre-treatment ciprofloxacin-resistant strain was isolated in 1/9 patients in whom eradication failed. Of 30 patients 29 completed the 2-week regimen; one patient experienced dizziness after 3 days of treatment. The most common side-effect was increased stool frequency (n = 6). This 2-week treatment regimen for metronidazole-resistant H. pylori is well tolerated and achieves an eradication rate of 70%. | {
"pile_set_name": "PubMed Abstracts"
} |
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