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Neural substrates for reversing stimulus-outcome and stimulus-response associations.
Adaptive goal-directed actions require the ability to quickly relearn behaviors in a changing environment, yet how the brain supports this ability is barely understood. Using functional magnetic resonance imaging and a novel reversal learning paradigm, the present study examined the neural mechanisms associated with reversal learning for outcomes versus motor responses. Participants were extensively trained to classify novel visual symbols (Japanese Hiraganas) into two arbitrary classes ("male" or "female"), in which subjects could acquire both stimulus-outcome associations and stimulus-response associations. They were then required to relearn either the outcome or the motor response associated with the symbols, or both. The results revealed that during reversal learning, a network including anterior cingulate, posterior inferior frontal, and parietal regions showed extended activation for all types of reversal trials, whereas their activation decreased quickly for trials not involving reversal, suggesting their role in domain-general interference resolution. The later increase of right ventral lateral prefrontal cortex and caudate for reversal of stimulus-outcome associations suggests their importance in outcome reversal learning in the face of interference.
18,971,462
Online contributions of auditory feedback to neural activity in avian song control circuitry.
Birdsong, like human speech, relies critically on auditory feedback to provide information about the quality of vocalizations. Although the importance of auditory feedback to vocal learning is well established, whether and how feedback signals influence vocal premotor circuitry has remained obscure. Previous studies in singing birds have not detected changes to vocal premotor activity after perturbations of auditory feedback, leading to the hypothesis that contributions of feedback to vocal plasticity might rely on"offline" processing. Here, we recorded single and multiunit activity in the premotor nucleus HVC (proper name) of singing Bengalese finches in response to feedback perturbations that are known to drive plastic changes in song. We found that transient feedback perturbation caused reliable decreases in HVC activity at short latencies (20-80 ms). Similar changes to HVC activity occurred in awake, nonsinging finches when the bird's own song was played back with auditory perturbations that simulated those experienced by singing birds. These data indicate that neurons in avian vocal premotor circuitry are rapidly influenced by perturbations of auditory feedback and support the possibility that feedback information in HVC contributes "online" to the production and plasticity of vocalizations.
18,971,480
Characteristics associated with longer breastfeeding duration: an analysis of a peer counseling support program.
Breastfeeding peer counseling support programs for low-income women have been implemented across the United States. Data from one such program were used to examine participant and program characteristics, of those enrolled prenatally (n = 2168) or postnatally (n = 2899), and to determine how these characteristics affected breastfeeding outcomes. Shorter breastfeeding duration was significantly predicted by introduction of formula on day 1 postpartum in participants enrolled prenatally (-37.9 days [95% CI: -57.9 to -17.9]) as well as postnatally (-49.1 days [95% CI: -63.4 to -34.8]). In both groups, increasing maternal age and previous breastfeeding experience were associated with significantly longer breastfeeding duration. Breastfeeding duration may be improved in programs by targeting younger mothers, those without breastfeeding experience, and focusing on delaying the introduction of formula.
18,971,503
Effects of the Y chromosome on cardiovascular risk factors in Japanese men.
Excess cardiovascular risk in men compared with women has been suggested to be partly explained by effects of the Y chromosome. However, inconsistent results have been reported on the Y chromosome's genetic influence on blood pressure and lipid levels. The purpose of the present study was to settle the question whether genetic variants of the Y chromosome influence cardiovascular risk factors using a large epidemiological cohort, the Suita study. Possible influences of the Y chromosome polymorphisms (Y chromosome Alu insertion polymorphism [YAP], M175 and SRY+465) on cardiovascular risk factors were assessed in 974 Japanese men. The frequency of the YAP(+) allele in our study sample was 0.31. The prevalence of hypertension tended to be higher in YAP(+) than in YAP(-) men, and this tendency was found to be stronger among men aged 65 years or older. Men with the YAP(+) genotype had higher levels of high density lipoprotein (HDL) cholesterol compared with those with the YAP(-) genotype, even after adjustment for age, body mass index, and daily ethanol and cigarette consumption (57.0+/-14.6 mg/dL vs. 54.2+/-14.2 mg/dL, nominal p=0.011, adjusted p=0.0062). However, these observed nominal associations disappeared after adjusting for multiple testing (Bonferroni). No association was detected between the YAP genotype and myocardial infarction. Similarly, none of the associations with M175 and SRY+465 attained significance when multiple testing was taken into account. In conclusion, Y chromosome polymorphisms (YAP, M175 and SRY+465) do not appear to be associated with cardiovascular risk factors in Japanese men. Studies using much larger sample sizes and/or additional independent samples will be required for definitive conclusions.
18,971,546
Risk factors for cesarean delivery in preterm, term and post-term patients undergoing induction of labor with an unfavorable cervix.
To identify risk factors for cesarean delivery in patients with an unfavorable cervix undergoing an indicated induction of labor. This is a secondary analysis of combined data from three prospective randomized trials comparing cervical ripening methods in singleton pregnancies with an unfavorable cervix seeking to identify risk factors for cesarean delivery. Nine hundred and five women underwent an induction of labor for a variety of indications. Gestational age ranged from 27.0-42.8 weeks (mean of 37.8 weeks) and initial Bishop's score from 0-6 (mean 2.5). There were 613 vaginal deliveries (67.7%) and 292 cesarean deliveries (32.2%). Factors associated with an increased risk for cesarean delivery included nulliparous status, Bishop's score <or=1, body mass index >40 and diabetes mellitus. Risk factors for cesarean delivery in women undergoing an indicated induction include a low Bishop's score, high BMI, nulliparity and diabetes.
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Indocyanine green angiography in experimental choroidal circulatory disturbance.
To determine how choroidal venous congestion alters the indocyanine green angiograms (ICGA) of monkeys. Two vortex veins in each eye of 5 Japanese macaque monkeys were sutured and cauterized at their exit. ICGA and fluorescein angiography (FA) were performed immediately after the occlusions. The FA and ICGA findings were correlated with the histopathological changes. ICGA showed a delay in filling the choroidal arteries in the field of the occluded vortex veins, and the choroidal veins were filled retrogradely in a pulsatile manner. The fluorescence intensity of the larger veins was higher in the occluded area. The clearance of the indocyanine green dye was delayed by approximately 15 min. Histology showed that the choroidal veins in the occluded field were engorged with red blood cells. The ICGA findings in eyes with choroidal venous congestion are a delay in the filling of the choroidal arteries, reflux of venous blood flow, increase in fluorescence intensity of the choroidal veins, and delayed indocyanine green dye clearance.
18,971,589
[Evaluation of multiplex PCR assay using dual priming oligonucleotide system for detection mutation in the Duchenne muscular dystrophy gene].
Exon deletions of Duchenne muscular dystrophy (DMD) gene account for most of the alterations found in DMD and Becker muscular dystrophy (BMD). This study was to evaluate the usefulness of dual priming oligonucleotide multiplex PCR (DPO PCR) in detection of exon deletions of DMD gene. Thirty-seven DMD or BMD patients who had known exon deletions detected by conventional multiplex PCR (conventional PCR) and nine control subjects were enrolled in this study. When a discrepancy was shown between the results of conventional PCR and DPO PCR, the multiplex ligation-dependent probe amplification (MLPA) technique was performed as a confirmation test. The same deletions previously identified by conventional PCR in 32 out of 37 subjects were also detected by DPO PCR. For the five subjects (13.5%) showing discrepant results between the conventional PCR and DPO PCR, MLPA was performed and its results were found to correlate better with those of DPO PCR. The discrepancies were due to false positive or false negative results of the conventional PCR. DPO PCR shows a high agreement of results with the conventional PCR and is considered an adequate method to be used as a primary genetic test for the diagnosis of DMD. Because of an improved accuracy, especially for determining the boundaries of DMD gene deletions, DPO PCR can be very useful as a supplement to the conventional PCR.
18,971,620
Brain energetics (thought needs food).
Almost 15 years after its initial proposal, the astrocyte-neuron lactate shuttle hypothesis still occupies the center stage in research on brain energetics. Recent developments have provided further evidence for its validity and have extended its application to different areas of neuroscience. Description of cell-specific metabolic characteristics have reinforced the view that a prominent conversion of glucose into lactate takes place in astrocytes, whereas neurons preferentially take up and oxidize lactate over glucose-derived pyruvate. Indeed, specific mechanisms are activated by glutamatergic activity to favor such a net lactate transfer between the two cell types. Moreover, demonstration in vivo of the existence and implication of the astrocyte-neuron lactate shuttle hypothesis for particular neurophysiological processes is beginning to appear. Brain energetics has undertaken its revolution. A new concept based on metabolic compartmentalization between astrocytes and neurons is establishing itself as the leading paradigm that opens new perspectives in areas such as functional brain imaging and regulation of energy homeostasis.
18,971,641
The role of Title VII funding in academic general pediatrics fellowships and leadership.
Since 1979, the Health Resources and Services Administration, Bureau of Health Professionals Title VII, Section 747 (Title VII) programs have been critical to both fellowship and leadership training in academic general pediatrics. Title VII-funded faculty development programs and targeted contract funding have played an important role in training pediatric academic generalist faculty, supporting individual fellowship programs, defining the core elements of such programs, and expanding faculty development to include leadership training. As the major continuing source of external funding for these programs, Title VII has produced documented successful outcomes in all areas in terms of both numbers and accomplishments of trainees. Title VII-funded fellows, as well as the leaders trained, have formed and extended the field of general pediatrics, ultimately improving the health of children, especially in underserved and vulnerable populations.This article is part of a theme issue of Academic Medicine on the Title VII health professions training programs.
18,971,667
Osteoporosis: how long should we treat?
Bisphosphonates are the most commonly used treatment for osteoporosis. The pharmacology of bisphosphonates suggests the possibility of discontinuing treatment for a period, and patients frequently ask about this. In an attempt to help answer these questions, this review will consider recent data relevant to continuing and discontinuing long-term bisphoshonate therapy and other osteoporosis therapy. Morphometric vertebral fracture protection continues for 1 year after discontinuation of risedronate for 3 years and there are now similar bishosphonate data for hip fractures. Nonvertebral fractures -in high-risk women - and perhaps clinical vertebral fractures may be reduced in women treated for 10 years with alendronate compared with those who stopped treatment after 5 years. After discontinuing bisphosphonates, bone mineral density appears to deplete more rapidly in the spine than in the hip and biochemical markers appear to increase. These changes occur very rapidly after discontinuing denosumab. Fractures at unusual sites have been reported with long-term bisphosphonate use. It appears that a drug holiday can be considered in many patients, although high-risk patients may benefit from continued bisphosphonate therapy. Recent unusual fracture cases need to be considered in making long-term treatment decisions.
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Nasal reconstruction with local flaps: a simple algorithm for management of small defects.
After studying this article, the participant should: 1. Be familiar with subunits of the nose. 2. Understand various flaps used in nasal reconstruction. 3. Be able to choose a flap for the defect depending on its location, size, shape and orientation. Management of small defects in nasal reconstruction can be quite challenging. Location, size, shape, and orientation of the defects are important factors in determining the method used in reconstruction. In this article, the authors retrospectively examined 300 cases where local flaps were used to reconstruct small nasal defects. The authors correlated the characteristics of those defects with the techniques used to reconstruct them. The authors found that certain flaps were used predominantly in reconstruction of certain defects. The authors were able to develop a simple algorithm for management of small nasal defects that may prospectively aid the planning of reconstructive strategy in these cases.
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Avoiding denervation of rectus abdominis in DIEP flap harvest II: an intraoperative assessment of the nerves to rectus.
The deep inferior epigastric artery perforator (DIEP) flap aims to reduce donor-site morbidity by minimizing rectus muscle damage; however, damage to motor nerves during perforator dissection may denervate rectus muscle. Although cadaveric research has demonstrated that individual nerves do not arise from single spinal cord segments and are not distributed segmentally, the functional distribution of individual nerves remains unknown. Using intraoperative nerve stimulation, the current study describes the motor distribution of individual nerves supplying the rectus abdominis, providing a guide to nerve dissection during DIEP flap harvest. Twenty rectus abdominis muscles in 17 patients undergoing reconstructive surgery involving rectus abdominis (DIEP, transverse rectus abdominis musculocutaneous, or vertical rectus abdominis musculocutaneous flaps) underwent intraoperative stimulation of nerves innervating the infraumbilical segment of the rectus. Nerve course and extent of rectus muscle contraction were recorded. In each case, three to seven nerves entered the infraumbilical segment of the rectus abdominis. Small nerves (type 1) innervated small longitudinal strips of rectus muscle, rather than transverse strips as previously described. There was significant overlap between adjacent type 1 nerves. In 18 of 20 cases, a single large nerve (type 2) at the level of the arcuate line supplied the entire width and length of rectus muscle. Nerves innervating the rectus abdominis are at risk during DIEP flap harvest. Small, type 1 nerves have overlapping innervation from adjacent nerves and may be sacrificed without functional detriment. However, large type 2 nerves at the level of the arcuate line innervate the entire width of rectus muscle without adjacent overlap and may contribute to donor-site morbidity if sacrificed.
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Motility differences in free colon and free jejunum flaps for reconstruction of the cervical esophagus.
Free colon and jejunal flaps have been described as reliable and safe conduits for pharyngoesophageal reconstruction. Compared with free colon flaps, free jejunum flaps have a smaller diameter and intrinsic peristaltic movement, both of which are considered possible causes of dysphagia. In this investigation, the authors evaluated motility differences in free jejunum and colon flaps using radionuclide esophageal scintigraphy. Patients who received free jejunum flaps (n = 12) or free colon (n = 1) or ileocolon flaps (n = 13) for reconstruction after pharyngoesophagectomy for cancer were included. Radionuclide esophageal scintigraphy was performed using technetium-99m-labeled sulfur colloid. Transit rate was evaluated at 1 second (pharyngeal or initial clearance) and 10 seconds (esophageal or clearance throughout). Clinical progression of swallowing was recorded postoperatively. Statistical analysis was performed using the t test. Mean pharyngeal clearance was 61 +/- 20 percent for free colon and ileocolon flaps and 70 +/- 16 percent for free jejunum flaps. Mean esophageal clearance was 50 +/- 27 percent for free colon and ileocolon flaps and 69 +/- 17 percent for free jejunum flaps. Esophageal transit rate was significantly shorter in patients who underwent reconstruction with free jejunum flaps (p = 0.04). At 1 year, 10 of 12 free jejunum patients and eight of 14 patients were tolerating solid foods. Although neither flap showed normal swallowing characteristics, free jejunum flaps displayed greater esophageal clearance and should represent the first choice in hypopharyngeal reconstruction. Free colon and ileocolon flaps should be reserved for very proximal oropharyngeal defects and when simultaneous voice reconstruction is desired.
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Diastasis recti: clinical anatomy.
Enduring diastasis repair is one of the yardsticks by which a successful abdominoplasty is measured, because the presence and size of diastasis recti are thought to be reliable indicators of abdominal wall laxity and protrusion. The author's study of the "normal" anatomy of diastasis challenges these concepts about diastasis recti. Ninety-two consecutive abdominoplasty patients, in whom intraoperative measurements of the linea alba were taken, were included in this study. The degree of abdominal wall protrusion was quantified by estimating the intra-abdominal fat volume in the upright patient as large, medium, or small. The most striking anatomical finding was that the linea alba has a limited range of stretch, most commonly between 1 and 2 inches, regardless of the extent of the abdominal girth. Moreover, eight patients with diastasis did not manifest abdominal protrusion, and in five patients, diastasis was absent, although a significant protrusion was present. Also, the site of the widest diastasis (supraumbilical/infraumbilical) frequently did not correspond to the site of the protrusion. Contrary to current thought, abdominal wall protrusions are caused by the stretching of the entire abdominal wall and not only the linea alba. Thus, significant abdominal wall protrusions may occur without diastasis and flat abdomens may exhibit a diastasis. Abdominal protrusion should replace diastasis as the prime indicator of abdominal wall laxity; stretching and the decision to perform diastasis repair should be influenced primarily by the evaluation of the protrusion rather than the diastasis.
18,971,741
Return to work after spinal cord injury: is it related to wheelchair capacity at discharge from clinical rehabilitation?
To describe the number of people with spinal cord injury who returned to work (RTW) 1 yr after discharge from inpatient rehabilitation and to investigate whether RTW can be predicted from wheelchair capacity at discharge from inpatient rehabilitation, after correction for confounders. Prospective cohort study in which 118 subjects with spinal cord injury (age 18-65 yrs) of eight Dutch rehabilitation centers participated. Main outcome measure was RTW for at least 1 hr/wk. The outcome variables of wheelchair capacity were peak oxygen uptake, peak aerobic power output, and wheelchair skill scores (ability, performance time, and physical strain). Possible confounders were age, gender, lesion level, and lesion completeness. Where necessary, corrections were made for education level. Thirty-three percent of the subjects RTW. Peak aerobic power output (persons with a 10-W higher peak aerobic power output were 1.37 times more likely to RTW), ability score (persons with a one-point higher ability score were 2.22 times more likely to RTW), and performance time (an increase, or worsening, of 1 sec on the performance time gave an odds ratio of 0.87, so persons with lower, or better, performance time scores were more likely to RTW) were significant predictors of RTW after correction for confounders and education level. RTW was successful in 33% of the subjects. Wheelchair capacity was independently related to RTW. Therefore, it is recommended to train wheelchair capacity in the context of RTW.
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Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer.
Tumor budding along the advancing front of colorectal adenocarcinoma is an early event in the metastatic process. A reproducible, prognostic budding scoring system based on outcomes in early stage colorectal cancer has not been established. One hundred twenty-eight T3N0M0 colorectal carcinoma patients with known outcome were identified. Tumor budding was defined as isolated tumor cells or clusters of <5 cells at the invasive tumor front. Tumor bud counts were generated in 5 regions at 200x by 2 pathologists (conventional bud count method). The median bud count per case was used to divide cases into low (median=0) and high budding (median > or =1) groups. Forty cases were reevaluated to assess reproducibility using the conventional and a novel rapid bud count method. Fifty-seven (45%) carcinomas had high and 71 (55%) had low budding scores. High budding was associated with an infiltrative growth pattern (P<0.0001) and lymphovascular invasion (P=0.005). Five-year cancer-specific survival was significantly poorer in high compared with low budding groups: 63% versus 91%, respectively, P<0.0001. Multivariate analysis demonstrated tumor budding to be independently prognostic (hazard ratio=4.76, P<0.001). Interobserver agreement was at least equivalent comparing the conventional to the rapid bud count methods: 87.5% agreement (kappa=0.75) versus 92.5% agreement (kappa=0.85), respectively. Tumor budding is a strong, reproducible, and independent prognostic marker of outcome that is easily assessed on hematoxylin and eosin slides. This may be useful for identifying the subset of T3N0M0 patients at high risk of recurrence who may benefit from adjuvant therapy.
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[Thrombo-embolic risks and bevacizumab: data from the literature and recommendations for the use of anticoagulants and antiaggregants].
Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. The use of bevacizumab has shown survival benefit in variety of cancers. However, a specific toxicity profile has been observed with bevacizumab such as hypertension, proteinuria, gastrointestinal perforation and arterial thrombosis. Non-small-cell lung cancer is often associated with thrombotic event therefore guidelines are expected to prescribe bevacizumab in this population. This article presents data from literature about the thrombotic risk and provides recommendations for the use of anticoagulant and antiaggregant treatments.
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[Early-stage NSCLC. The renaissance of radiotherapy in early-stage non-small cell lung cancer].
Surgery is the current standard treatment of early-stage non-small cell lung cancer (stage I and II tumors). Contrary to adjuvant chemotherapy, which was recently demonstrated to decrease systemic tumor recurrences as well as increasing overall survival, postoperative radiotherapy did not benefit from an actualized evaluation including the recent evolutions in radiation concepts and techniques. Available reported data have thus to be cautiously interpreted, taking into consideration that radiotherapy as described in ancient reports has not much left in common with current radiation modalities and techniques. Given the efficacy of chemoradiation in locally advanced non-small cell lung cancer, investigators may take advantage of the ongoing reevaluation of the role of postoperative radiotherapy to consider combinations with chemotherapy a potential therapeutic strategy in this setting. Moreover, technical improvements in radiation delivery, including stereotactic radiotherapy, allow the future development of new indications in early-stage tumors. More than ever, radiotherapy is one of the most promising therapeutic option for lung cancer.
18,971,830
[Satisfaction and compliance of ocular hypertensive and glaucoma patients topically treated with a combination therapy].
To evaluate satisfaction and compliance in glaucoma and ocular hypertensive patients receiving a fixed combination treatment. After instilling a fixed combination, patients were asked to fill out a questionnaire about their satisfaction and compliance at baseline and 15 days after the onset of new therapy. 1693 glaucoma patients (G) and 621 ocular hypertensive (OHT) patients were included. Mean age was 65.6+/-11.7 years. Onset of disease was 7.2+/-6.6 years and 5.2+/-4.9 years for G and OHT patients, respectively. Insufficient efficacy of the previous topical treatment (monotherapy in 55% of cases) was the main cause for shifting to a fixed combination in 70% of cases. Satisfaction was increased in 15% of the patients and compliance was increased in 25% of the patients. Fixed combination provides an easier regimen and therefore encourages better compliance, a key issue in a chronic disease such as glaucoma.
18,971,850
Behavioral and psychological symptoms and the progression of dementia of the Alzheimer type in nursing home residents.
Behavioral and psychological symptoms are common in the course of dementia of the Alzheimer's type (DAT). Some behavioral and psychological symptoms may be predictors of the progression of dementia and cognitive impairment in DAT. However, studies on this topic face serious methodological problems. The aim of our study was to investigate how aggressive and impulsive behaviors correlate with the progression of dementia and related cognitive impairments in DAT patients. Using the Cohen-Mansfield Agitation Inventory (CMAI) and the ADAS-cog we examined 39 nursing home residents diagnosed with mild to moderate DAT. Of these participants, 26 were re-evaluated with the ADAS-cog two years after baseline. Aggressive and impulsive behaviors correlated with the degree of cognitive impairment. However, we also found that particular ADAS-cog items correlated differently with the CMAI score. Moreover, various CMAI categories were differently related to cognitive disorders. Impairments in cognitive functioning best explain the fluctuations of verbal aggression and physical agitation (non-aggressive). At baseline, the more demented subjects had a higher general score on the CMAI scale and showed greater rates of physical aggression, verbal aggression and non-aggressive physical agitation. Particular items of the CMAI scale significantly differentiated our subjects in terms of progression of cognitive impairment. Aggressive behaviors in patients with DAT are linked to both the severity of dementia and the rate of its progression. At the same time, significant differences were noted with respect to particular behaviors.
18,971,872
Recurrent respiratory infections: why not talking about it any more?
Recurrent respiratory infections (RRIs) are a common and benign condition affecting about 6% of schoolchildren. Only mild, likely postinfective, modifications of the immune system have been proven, and parents should be reassured that the condition is self-limited. Nevertheless, if not correctly diagnosed, children may undergo several unnecessary investigations and multiple antibiotic courses. On the other hand, in some cases, efforts should be made to identify promptly possible underlying disease, including congenital or acquired immunodeficiency, vascular or airways malformation, tuberculosis, cystic fibrosis, or immotile-cilia syndrome. Careful medical history and clinical examination are usually sufficient to distinguish RRIs and no further research is generally needed. In uncertain cases a complete blood count with differential and the evaluation of total immunoglobulin serum levels are sufficient to exclude neutropenia, T- or B-lymphocyte defects, and selective IgA deficiency. It is essential to observe environmental risk factors: reducing environmental tobacco smoke at home is a fundamental goal and the postponed enrolment of children at day-care centres reduces the risk of RRIs. Antibiotic treatment are not justified since they do not shorten the course of the condition or prevent complications. Use of anti-cough syrups should be avoided. Nasal lavage with saline serum and the blowing are the only justified interventions. Adenoidectomy and tonsillectomy should be planned only in conditions included in validated guidelines.
18,971,902
Markers of acute coronary syndrome in emergency room.
Acute coronary syndromes (ACS) encompasses a spectrum of coronary heart diseases, ranging in severity from unstable angina to ST-elevation myocardial infarction (STEMI). Early diagnosis and risk stratification are needed in order to address correctly hospitalization and treatment. Although the diagnosis of STEMI in the presence of typical electrocardiogram (ECG) changes and symptoms is easy and does not require the use of biomarkers, cardiac biomarkers are particularly important in the Emergency Department (ED), where about 25% of patients admitted are affected by ACS but clinical presentation is often atypical and ECG alterations may be absent. The ideal marker in the ED should have rapid release, high sensitivity and specificity and risk stratifying properties. Classic cardiac biomarkers, like myoglobin, cardiac troponin T or I and creatine kinase-MB, have a poor sensitivity, dependent on the time past from the onset of symptoms to presentation, the duration of ischemia and the amount of myocardial tissue involved. Although the serial testing of these cardiac biomarkers can improve the detection of myocardial necrosis, there is still a need for the development of early markers that can reliably rule out ACS from the ED at presentation and also detect myocardial ischemia in the absence of irreversible myocyte injury. There are several markers which represent the different features of ACS pathogenesis and that can be divided into three major groups: markers of cardiac ischemia and necrosis, markers of inflammation and coronary plaque instability and marker of cardiac function.
18,971,915
Prevalence of selected risk behaviors and chronic diseases--Behavioral Risk Factor Surveillance System (BRFSS), 39 steps communities, United States, 2005.
Behavioral risk factors (e.g., tobacco use, poor diet, and physical inactivity) can lead to chronic diseases. In 2005, of the 10 leading causes of death in the United States, seven (heart disease, cancer, stroke, chronic lower respiratory diseases, diabetes, Alzheimer's disease, and kidney disease) were attributable to chronic disease. Chronic diseases also adversely affect the quality of life of an estimated 90 million persons in the United States, resulting in illness, disability, extended pain and suffering, and major limitations in daily living. 2005. CDC's Steps Program funds 40 selected U.S. communities to address six leading causes of death and disability and rising health-care costs in the United States: obesity, diabetes, asthma, physical inactivity, poor nutrition, and tobacco use. In 2005, a total of 39 Steps communities conducted a survey to collect adult health outcome data. The survey instrument was a modified version of the Behavioral Risk Factor Surveillance System (BRFSS) survey, a community-based, random-digit--dialing telephone survey with a multistage cluster design. The survey instrument collected information on health risk behaviors and preventive health practices among noninstitutionalized adults aged >/=18 years. Prevalence estimates of risk behaviors and chronic conditions varied among the 39 Steps communities that reported data for 2005. The proportion of the population that achieved Healthy People 2010 (HP 2010) objectives also varied among the communities. The estimated prevalence of obesity (defined as having a body mass index [BMI] of >/=30.0 kg/m(2) as calculated from self-reported weight and height) ranged from 15.6% to 44.0%. No communities reached the HP2010 objective of reducing the proportion of adults who are obese to 15.0%. The prevalence of diagnosed diabetes (excluding gestational diabetes) ranged from 4.3% to 16.6%. Eighteen communities achieved the HP2010 objective to increase the proportion of adults with diabetes who have at least an annual foot examination to 75.0%; five communities achieved the HP2010 objective to increase the proportion of adults with diabetes who have an annual dilated eye examination to 75.0%. The prevalence of reported asthma ranged from 7.0% to 17.6%. Among those who reported having asthma, the prevalence of having no symptoms of asthma during the preceding 30 days ranged from 15.4% to 40.3% for 10 communities with sufficient data for estimates. The prevalence of respondents who engaged in moderate physical activity for >/=30 minutes at least five times a week or who reported vigorous physical activity for >/=20 minutes at least three times a week ranged from 42.0% to 62.2%. The prevalence of consumption of fruits and vegetables at least five times a day ranged from 15.6% to 30.3%. The estimated prevalence among respondents aged >/=18 years who reported having smoked >/=100 cigarettes in their lifetime and who were current smokers on every day or some days at the time of the survey ranged from 11.0% to 39.7%. One community achieved the HP2010 objective to reduce the proportion of adults who smoke to 12.0%. Among smokers, the prevalence of having stopped smoking for >/=1 day as a result of trying to quit smoking during the previous 12 months ranged from 47.8% to 63.3% for 31 communities. No communities reached the HP2010 objective of increasing smoking cessation attempts by adult smokers to 75%. The findings in this report indicate variations in health risk behaviors, chronic conditions, and use of preventive health screenings and health services. These findings underscore the continued need to evaluate intervention programs at the community level and to design and implement policies to reduce morbidity and mortality caused by chronic disease. Steps BRFSS data can be used to monitor the prevalence of specific health behaviors, diseases, conditions, and use of preventive health services. Steps Program staff at the national, state, local, and tribal levels can use BRFSS data to demonstrate accountability to stakeholders, monitor progress in meeting program objectives, focus programs on activities with the greatest promise of results, identify opportunities for strategic collaboration, and identify and disseminate successes and lessons learned.
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Hormonal regulation of hepatic drug-metabolizing enzyme activity during adolescence.
Activities of drug-metabolizing enzymes (DMEs) are known to change throughout the course of physical and sexual maturation, with the greatest variability noted during infancy and adolescence. The mechanisms responsible for developmental regulation of DME are currently unknown. However, the hormonal changes associated with puberty/adolescence provide a theoretical framework for understanding the biochemical regulation of DME activity during growth and maturation. Important information regarding potential influences of growth and sex hormones can also be extrapolated from studies that evaluate changes in activities of DMEs occurring as a consequence of physiological, pathological, and/or pharmacological hormonal fluctuations. Collectively, current data support the hypothesis that isoform-specific alterations in DME activity during adolescence are mediated by sex and/or growth hormones. Characterization of the underlying biochemical alterations responsible for developmental changes in DME activity will require additional studies in which relationships between DMEs and important hormonal axes are evaluated during the course of pubertal development.
18,971,926
Brain metabolism dictates the polarity of astrocyte control over arterioles.
Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E(2), leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation.
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Safety and pharmacokinetics of motesanib in combination with gemcitabine for the treatment of patients with solid tumours.
The aim of this open-label phase 1b study was to assess the safety and pharmacokinetics of motesanib in combination with gemcitabine in patients with advanced solid tumours. Eligible patients with histologically or cytologically documented solid tumours or lymphoma were enroled in three sequential, dose-escalating cohorts to receive motesanib 50 mg once daily (QD), 75 mg two times daily (BID), or 125 mg QD in combination with gemcitabine (1000 mg m(-2)). The primary end point was the incidence of dose-limiting toxicities (DLTs). Twenty-six patients were enroled and received motesanib and gemcitabine. No DLTs occurred. The 75 mg BID cohort was discontinued early; therefore, 125 mg QD was the maximum target dose. Sixteen patients (62%) experienced motesanib-related adverse events, most commonly lethargy (n=6), diarrhoea (n=4), fatigue (n=3), headache (n=3), and nausea (n=3). The pharmacokinetics of motesanib and of gemcitabine were not markedly affected after combination therapy. The objective response rate was 4% (1 of 26), and 27% (7 of 26) of patients achieved stable disease. In conclusion, treatment with motesanib plus gemcitabine was well tolerated, with adverse event and pharmacokinetic profiles similar to that observed in monotherapy studies.
18,971,935
Chk2-dependent phosphorylation of XRCC1 in the DNA damage response promotes base excision repair.
The DNA damage response (DDR) has an essential function in maintaining genomic stability. Ataxia telangiectasia-mutated (ATM)-checkpoint kinase 2 (Chk2) and ATM- and Rad3-related (ATR)-Chk1, triggered, respectively, by DNA double-strand breaks and blocked replication forks, are two major DDRs processing structurally complicated DNA damage. In contrast, damage repaired by base excision repair (BER) is structurally simple, but whether, and how, the DDR is involved in repairing this damage is unclear. Here, we demonstrated that ATM-Chk2 was activated in the early response to oxidative and alkylation damage, known to be repaired by BER. Furthermore, Chk2 formed a complex with XRCC1, the BER scaffold protein, and phosphorylated XRCC1 in vivo and in vitro at Thr(284). A mutated XRCC1 lacking Thr(284) phosphorylation was linked to increased accumulation of unrepaired BER intermediate, reduced DNA repair capacity, and higher sensitivity to alkylation damage. In addition, a phosphorylation-mimic form of XRCC1 showed increased interaction with glycosylases, but not other BER proteins. Our results are consistent with the phosphorylation of XRCC1 by ATM-Chk2 facilitating recruitment of downstream BER proteins to the initial damage recognition/excision step to promote BER.
18,971,944
Another role of proline: stabilization interactions in proteins and protein complexes concerning proline and tryptophane.
Proline-tryptophan complexes derived from experimental structures are investigated by quantum chemical procedures known to properly describe the London dispersion energy. We study two geometrical arrangements: the "L-shaped", stabilized by an H-bond, and the "stacked-like", where the two residues are in parallel orientation without any H-bond. Interestingly, the interaction energies in both cases are comparable and very large ( approximately 7 kcal mol(-1)). The strength of stabilization in the stacked arrangement is rather surprising considering the fact that only one partner has an aromatic character. The interaction energy decomposition using the SAPT method further demonstrates the very important role of dispersion energy in such arrangement. To elucidate the structural features responsible for this unexpectedly large stabilization we examined the role of the nitrogen heteroatom and the importance of the cyclicity of the proline residue. We show that the electrostatic interaction due to the presence of the dipole, caused by the nitrogen heteroatom, contributes largely to the strength of the interaction. Nevertheless, the cyclic arrangement of proline, which allows for the largest amount of dispersive contact with the aromatic partner, also has a notable-effect. Geometry optimizations carried out for the "stacked-like" complexes show that the arrangements derived from protein structure are close to their gas phase optimum geometry, suggesting that the environment has only a minor effect on the geometry of the interaction. We conclude that the strength of proline non-covalent interactions, combined with this residue's rigidity, might be the explanation for its prominent role in protein stabilization and recognition processes.
18,972,023
The effect of methylprednisolone on treatment in rats with induced sepsis.
In this study, an appropriate sepsis model was created in rats. Additionally, the effects of steroid treatments on survival, in connection with antibiotic treatment, were investigated. The sepsis model performed via intraperitoneal injection of 3 ml/kg fecal suspension was determined as the most appropriate model for our study. Fifteen rats were used to investigate the effect of piperacillin-tazobactam on sepsis treatment. Forty-five randomly selected rats were used to investigate the efficacy of the antibiotic-plus-steroid combination. The rats were divided into three groups of 15 rats each. Twelve hours after the administration of fecal suspension, methylprednisolone (MP) at the dose of 0.25, 0.5, and 2 mg/kg/day was given to each group, respectively, in addition to an antibiotic administered intravenously. In order to investigate the effect of steroids alone in the treatment of sepsis, 0.5 mg/kg/day MP was given intravenously to 15 rats, 12 h after the fecal suspension was administered. It was concluded that administration of MP alone shortens survival time in rats with sepsis, whereas antibiotic therapy alone increases survival time significantly in rats with sepsis. It was seen that the antibiotic-plus-steroid treatment increases survival significantly compared to rats with no treatment (p < 0.05). In addition, steroids, when added to an antibiotic treatment in sepsis, affect survival positively when compared to the group with antibiotic therapy alone, depending on the dose given. Although, not statistically significant, high doses decrease survival (p > 0.05), and very low doses increase survival and mean survival time (p > 0.05) on the basis of clinical observation and average life time. However, low doses were found to increase survival significantly (p < 0.05). We concluded that low-dose MP, in addition to the appropriate antibiotic therapy, is the optimal in the treatment of rats with intraabdominal sepsis.
18,972,065
Behavioral indices in medical care outcome: the working alliance, adherence, and related factors.
The working alliance has been shown to be a consistent predictor of patient outcome and satisfaction in psychotherapy. This study examines the role of the working alliance and related behavioral indices in predicting medical outcome. Cognitive and emotional dimensions of the physician-patient relationship were examined in relation to patients' ratings of physician empathy, physician multicultural competence, perceived utility of treatment, and patients' adherence self-efficacy. These factors were then examined as part of a theoretical framework using path analyses to explain patient self-reported adherence to and satisfaction with treatment. The study was based on an ex-post facto field correlation design. One hundred fifty-two adult outpatients from a neurology clinic at Bellevue Hospital, a large municipal hospital in New York City, participated in the study. Surveys given to participants. We used the following measurements: Physician-Patient Working Alliance Scale, Perceived Utility Scale, Treatment Adherence Self-Efficacy Scale, Medical Outcome Study Adherence Scale, Physician Empathy Questionnaire, Physician Multicultural Competence Questionnaire, Medical Patient Satisfaction Questionnaire. The effect sizes for adherence are between 0.07 and 0.21 and for satisfaction between 0.10 to >0.50. Regression and path analyses showed that ratings of physician multicultural competence and patient adherence self-efficacy beliefs predicted patient adherence (SB = 0.34) and (SB = 0.30) and satisfaction (SB = 0.18) and (SB = 0.12), respectively. Working alliance ratings also predicted patient satisfaction (SB = 0.49). Psychological and interpersonal dimensions of medical care are related to patient adherence and satisfaction. Medical care providers may be able to use these dimensions to target and improve health care outcomes.
18,972,089
[Principles of the developmental process and implementation of guidelines. An update].
Guidelines are important tools to improve knowledge management, processes and outcomes in health care. Their function is to assist professionals and patients decisions about appropriate and effective practice, especially in those areas of health care where considerable variation or potential for improvement exists. The achievement of a favourable impact necessitates both a systematic and methodically sound approach in the development of guidelines. The German Instrument for Methodological Guideline Appraisal, an adopted and supplemented version of the AGREE (Appraisal of Guidelines Research and Evaluation) instrument, provides 34 quality criteria guideline developers should take into account. However, the impact of guidelines is not only determined by methodological soundness but also by the choice of the guideline topic (need for a guideline), by its dissemination (accessibility) and implementation (acceptance and use). Finally, this impact must be monitored by means of guideline-based quality indicators.
18,972,093
Inhaled milrinone attenuates experimental acute lung injury.
To test whether inhalation of the phosphodiesterase 3 inhibitor milrinone may attenuate experimental acute lung injury (ALI). In rats, ALI was induced by infusion of oleic acid (OA). After 30 min, milrinone was inhaled either as single dose, or repeatedly in 30 min intervals. In mice, ALI was induced by intratracheal instillation of hydrochloric acid, followed by a single milrinone inhalation. Four hours after OA infusion, ALI was evident as lung inflammation, protein-rich edema and hypoxemia. A single inhalation of milrinone attenuated the increase in lung wet-to-dry weight ratio and myeloperoxidase activity, and reduced protein concentration, neutrophil counts and TNF-alpha levels in bronchoalveolar lavage. This effect was further pronounced when milrinone was repeatedly inhaled. In mice with acid-induced ALI, milrinone attenuated hypoxemia and prevented the increase in lung myeloperoxidase activity. Inhalation of aerosolized milrinone may present a novel therapeutic strategy for the treatment of ALI.
18,972,099
[Glucocorticoids in rheumatology].
Glucocorticoids (GC) are effective drugs which are often used in rheumatology. However, they have a considerable potential for frequent and sometimes serious side effects that restrict their use. Their mechanisms of action are either receptor dependent (specific) or independent (unspecific) on the genomic as well as the non-genomic level. Many adverse effects are predominantly caused by transactivation while the desired effects are mostly mediated by transrepression. Treatment strategies are sub-classified into low, medium, high, very high dose and pulse therapy based on criteria such as dose, indication, duration of treatment and potential risk of adverse events. The musculoskeletal, gastrointestinal, neuro-endocrino-immunological, opthalmological and neuropsychiatric systems are examples where adverse effects may occur.
18,972,122
Imaging of hereditary hemorrhagic telangiectasia.
This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients.
18,972,161
An evaluation of four phylogenetic markers in Nostoc: implications for cyanobacterial phylogenetic studies at the intrageneric level.
The success of some phylogenetic markers in cyanobacteria owes to the design of cyanobacteria-specific primers, but a few studies have directly investigated the evolution "behavior" of the loci. In this study, we performed a case study in Nostoc to evaluate rpoC1, hetR, rbcLX, and 16S rRNA-tRNA(Ile)-tRNA(Ala)-23S rRNA internal transcribed spacer (ITS) as phylogenetic markers. The results indicated that the gene trees of these loci are not congruent with the phylogeny based on 16S rRNA gene. The mechanisms contributing to the incongruence include randomized variation and recombination. As the results suggested, one should be careful to choose the molecular markers for phylogenetic reconstruction at the intrageneric level in cyanobacteria.
18,972,163
Comparison of surgically resected polypoid lesions of the gallbladder to their pre-operative ultrasound characteristics.
Polypoid lesions of the gallbladder (PLG) have been a common finding on ultrasound examinations of the abdomen and are more prevalent since our use of equipment incorporating pulse shaping increased bandwidth, and enhanced phase use for image reconstruction began in 1996. Our study correlates the pre-operative ultrasonographic findings of these lesions to the surgically resected specimen with specific regard to identifying neoplastic polyps. A retrospective review was performed of 130 patients who had a pre-operative ultrasound of the gallbladder and subsequently underwent cholecystectomy between August 1996 and July 2007 at the Mayo Clinic Rochester. Seventy-nine pseudopolyps (cholesterol polyps, inflammatory polyps, and adenomyomas) and 15 neoplastic polyps were identified on histopathologic analysis. However, 36 patients (27%) did not have a PLG upon histopathologic analysis. Thirty-one polyps had suspicious ultrasonographic characteristics for neoplastic changes. Twenty-nine were > or = 10 mm, 12 had vascularity, and one demonstrated invasion. Of these, there were 23 pseudopolyps and six true polyps with neoplastic changes on final pathology (four dysplastic adenomas and two adenocarcinomas). Three asymptomatic polyps < or = 10 mm (4%) in maximum diameter based on pre-operative ultrasound imaging (US) had neoplastic changes at pathology (two dysplastic adenomas and one adenocarcinoma). Several statistically significant risk factors were identified that increased the likelihood for malignancy in a PLG: history of primary sclerosing cholangitis (PSC), local invasion, vascularity, and > or = 6 mm maximum diameter based on pre-operative US. Of PLGs < or = 10 mm, 7.4% were neoplastic. Twenty-five patients were followed up with at least two serial ultrasound examinations. Of these, seven demonstrated polyp growth. None of these specimens demonstrated neoplastic changes. The positive predictive value (PPV) and negative predictive value (NPV) for ultrasound diagnosing neoplastic changes based on current criteria was 28.5% and 93.1%, respectively, with a false negative rate of 5.0%. Expanding the criteria to include cholecystectomy for PLGs > or = 6 mm changes the positive predictive value and negative predictive value to 18.5% and 100%, respectively, with a false negative rate of 0%. Histopathologic analysis of polypoid lesions of the gallbladder continues to be the gold standard to identify malignancy. Ultrasound has been used extensively in the pre-operative management of these lesions, but modern ultrasound techniques are unable to differentiate between benign and malignant PLGs with any certainty. We recommend that strong consideration be given to surgical resection of PLGs > or = 6 mm based on pre-operative US due to the significant risk of neoplasm. Additionally, PLGs in all patients with PSC, any patient in whom diligent long-term follow-up cannot be completed, and lesions that demonstrate growth, vascularity, invasion, or are symptomatic require cholecystectomy.
18,972,168
Characteristics of mammography facility locations and stage of breast cancer at diagnosis in Chicago.
In the United States, despite substantial investment in public health initiatives to promote early detection of breast cancer through screening mammography, the proportion of female breast cancers that have advanced beyond the localized stage by the time of diagnosis remains high. Our objective in this exploratory study was to investigate whether stage of breast cancer at diagnosis among Chicago residents is associated with characteristics of the neighborhoods in which proximate mammography facilities are located. Those characteristics may influence likelihood of utilizing the service routinely and partly explain differences in stage at diagnosis. We used a retrospective cohort design and combined 3 years of data from the Illinois State Cancer Registry (ISCR) with information on locations of mammography facilities, public transportation service, crime, and area demographic and economic characteristics. Using a Geographic Information System (GIS), we identified the five facilities located nearest to each case's residence. Estimates of the association between characteristics of mammography facility locations and breast cancer stage at diagnosis were obtained using the partial proportional odds regression model. We found that the number of homicides in areas in which the nearest mammography facilities were located was associated with increased odds of later stage diagnosis. This effect was independent of age, race, and residential area education and income. We found no effect on stage of distance, public transportation service, or measures of neighborhood social similarity. The "spatial dynamics" of health may involve geographies beyond the immediate neighborhood. The results of our study suggest that areas in which the nearest mammography facilities are located may be one such geography. We hope that this study will spark research interest in the impact of health service locations on utilization.
18,972,211
Adrenal cystic lesions: a clinicopathological analysis of 25 cases with proposed histogenesis and review of the literature.
Adrenal cystic lesions are uncommon and we analyzed clinical and pathologic features of 25 such cases from a single institute over 23 years. There were 16 pseudocysts, eight endothelial cysts, and one epithelial cyst. Seven of eight endothelial cysts were confirmed to be lymphangiomatous by D2-40 immunostaining. We suggest that pseudocysts and endothelial cysts may have different histogenesis. The proposed mesothelial origin of adrenal epithelial cyst cannot be confirmed in our example. Seven adrenal pseudocysts were associated with tumor, including two pheochromocytomas, one neuroblastoma, one adrenal cortical carcinoma, one adrenal cortical adenoma, one myelolipoma, and one schwannoma. The distinction of true cystic lesion from cystic neoplasm is important and requires thorough sampling of the specimens.
18,972,224
Novel factor-loaded polyphosphazene matrices: potential for driving angiogenesis.
Currently employed bone tissue engineered scaffolds often lack the potential for vascularization, which may be enhanced through the incorporation of and regulated release of angiogenic factors. For this reason, the objective here was to fabricate and characterize protein-loaded amino acid ester polyphosphazene (Pphos)-based scaffolds and evaluate the novel sintering method used for protein incorporation, a method which will ultimately allow for the incorporation of proangiogenic agents. To test the hypothesis, Pphos and their composite microspheres with nanocrystalline hydroxyapatite (Pphos-HAp) were fabricated via the emulsion solvent evaporation method. Next, bovine serum albumin (BSA)-containing microsphere matrices were created using a novel solvent-non-solvent approach for protein loading. The resulting protein (BSA) loaded circular porous microsphere based scaffolds were characterized for morphology, porosity, protein structure, protein distribution and subsequent protein release pattern. Scanning electron microscopy revealed porous microsphere scaffolds with a smooth surface and sufficient level of sintering, illustrated by fusion of adjacent microspheres. The porosity measured for the poly(ethyl phenylalanato:glycinato)phosphazene (PNPhGly) and poly(ethyl phenylalanato:glycinato)phosphazene-hydroxyapatite (PNPhGly-HAp) scaffolds were 23 +/- 0.11% and 18 +/- 4.02%, respectively, and within the range of trabecular bone. Circular dichroism confirmed an intact secondary protein structure for BSA following the solvent sintering method used for loading and confocal microscopy verified that FITC-BSA was successfully entrapped both between adjacent microspheres and within the surface of the microspheres while sintering. For both Pphos and their composite microsphere scaffolds, BSA was released at a steady rate over a 21 day time period, following a zero order release profile. HAp particles in the composite scaffolds served to improve the release profile pattern, underscoring the potential of HAp for growth factor delivery. Moreover, the results of this work suggest that the solvent-non-solvent technique for protein loading is an optimal one that will allow for future development of angiogenic factor-loaded Pphos matrices with the capacity to invoke neovascularization.
18,972,247
The issue of consent in research that administers drugs of addiction to addicted persons.
In addiction, impaired control over drug use raises questions about the capacity of addicted persons to consent to participate in research studies in which they are given their drug of addiction. We review the case for doing such research, and the arguments that addiction does, and does not, prevent addicted persons from consenting to such research. We argue for a more nuanced view that acknowledges that while in some situations addiction impairs decision-making capacity, it does not eliminate such capacity. We conclude with some suggestions for recruiting addicted subjects and designing experiments in ways to obtain free and informed consent.
18,972,263
Biomedical research and the commercialization agenda: a review of main considerations for neuroscience.
This article reviews a range of issues associated with the commercialization of biomedical research and speculates on how these issues might apply to the neuroscience context. Drawing on existing studies of the impact of research commercialization activities on various areas of biotechnology research, the authors explore normative benchmarks for assessing and resolving issues likely to arise from the commercialization of neuroscientific research, including such topics as patenting, marketing pressures, and representations of research prospects.
18,972,268
Difference in airflow obstruction between Hispanic and non-Hispanic White female smokers.
Smoking-related respiratory diseases are a major cause of morbidity and mortality. However, the relationship between smoking and respiratory disease has not been well-studied among ethnic minorities in general and among women in particular. The objective of this cross-sectional study was to evaluate the risk of airflow obstruction and to assess lung function among Hispanic and non-Hispanic White (NHW) female smokers in a New Mexico cohort. Participants completed a questionnaire detailing smoking history and underwent spirometry testing. Outcomes studied included airflow obstruction, selected lung function parameters, and chronic mucus hyper-secretion. Chi square, logistic, and linear regression techniques were utilized. Of the 1,433 eligible women participants, 248 (17.3%) were Hispanic; and 319 had airflow obstruction (22.3%). Hispanic smokers were more likely to be current smokers, and report lower pack-years of smoking, compared to NHW smokers (p < 0.05 for all analyses). Further, Hispanic smokers were at a reduced risk of airflow obstruction compared to NHW smokers, with an O.R. of 0.51, 95% C.I. 0.34, 0.78 (p = 0.002) after adjustment for age, BMI, pack-years and duration of smoking, and current smoking status. Following adjustment for covariates, Hispanic smokers also had a higher mean absolute and percent predicted post-bronchodilator FEV(1)/FVC ratio, as well as higher mean percent predicted FEV(1) (p < 0.05 for all analyses). Hispanic female smokers in this New Mexico-based cohort had lower risk of airflow obstruction and better lung function than NHW female smokers. Further, smoking history did not completely explain these associations.
18,972,275
The properties and functions of virus encoded microRNA, siRNA, and other small noncoding RNAs.
microRNAs (miRNAs) represent a class of noncoding RNA species, believed to be regulating gene expression by binding to complementary sites in the 3'UTRs of target mRNAs. They play important regulatory roles in various metabolic pathways in most eukaryotes. The recent discovery of virus encoded miRNAs suggests that viruses may be using them to regulate host and viral gene expression. Another class of closely related small interfering RNAs (siRNAs) also has been found within the HIV-1 genome and shown to be exerting a limited impact on virus reproduction. Additionally, an additional type of viral noncoding RNAs named small noncoding RNAs (sncRNAs) ranging from a few tens to a few hundred nucleotides in length, has also been identified. sncRNAs have a wide phylogenesis and high levels of expression, suggesting they may play an important roles in different species. Here we discuss the genomic organization, expression, conservation as well as potential function of virally encoded miRNA, siRNA, and sncRNAs.
18,972,284
Autobiographical memory in long-term survivors of severe traumatic brain injury.
The aim of this study was to examine the ability of persons who had sustained a severe traumatic brain injury (TBI) at least 6 years previously to recall memories associated with famous names. Each of 19 persons with TBI was matched with a healthy control of the same age, gender, and occupational-educational background. A list of 115 names of famous people was compiled, 25 of whom came to prominence in each decade from 1960 to 1999, and 15 in the period 2000 to 2005. Participants were first asked whether they recognized each name as being of a famous person and to state the reason for the individual's fame. For those names they correctly identified, they were asked to recall a memory associated with the person; each memory produced was categorized as a context-specific memory or a general memory. The ability to recognize and identify famous names was well preserved in the TBI group; however, they showed a consistent impairment in the ability to recall specific episodic memories acquired before and after the date of the TBI. This inability to generate personal and specific information is likely to have an impact on the ability of the person with TBI to participate in interpersonal interactions and problem solve in complex social situations.
18,972,310
Outcome measures in physiotherapy management of patients with stroke: a survey into self-reported use, and barriers to and facilitators for use.
OBJECTIVE. To investigate physiotherapists' self-reported use of outcome measures as recommended in the Dutch Clinical Practice Guideline on Physiotherapy Management of Patients with Stroke (CPGPS) and to assess perceived barriers to and facilitators for the use of outcome measures in everyday practice. A 41-item survey, including the barriers and facilitators questionnaire (BFQ), was sent by post to 400 physiotherapists in each of the following settings in the Netherlands: acute care hospitals (ACH; n = 100), rehabilitation centres (RC; n = 100), nursing homes (NH; n = 100) and private physiotherapy practices (PPP; n = 100). One hundred and eighty-nine physiotherapists returned the survey (47%; ACH, n = 57; RC, n = 67; NH, n = 26 and PPP, n = 39) and the surveys of 167 physiotherapists involved in stroke settings were analysed. These physiotherapists reported regularly using three (median; range 0-7) of the seven recommended outcome measures, with those working in RC or ACH reporting a significantly higher use than their colleagues in PPP (4 vs. 0 and 3 vs. 0; p < 0.001 and p = 0.02, respectively). The BFQ revealed that there were setting-specific facilitators, such as 'a positive attitude towards outcome measures' (as mentioned by 93% of the physiotherapists) and 'acquaintance with outcome measures' (90%), and barriers such as 'changing routines' (32%), 'time investment' (29%) and 'financial compensation' (21%). Despite an almost uniformly positive attitude, physiotherapists infrequently use the outcome measures recommended in the CPGPS. Robust setting-specific tailored implementation strategies based on the reported barriers and facilitators are needed.
18,972,323
Improved delayed enhanced myocardial imaging with T2-Prep inversion recovery magnetization preparation.
To develop a magnetization preparation method that improves the differentiation of enhancing subendocardial infarction (MI) from ventricular blood for myocardial delayed-enhancement (DE) magnetic resonance imaging (MRI). T2Prep-IR is a magnetization preparation pulse that consists of a T2 preparation (T2Prep) followed immediately by a nonselective inversion recovery (IR) pulse. The first imaging excitation is then delayed an inversion time (TI) to allow nulling of normal myocardium in DE study. The amount of T2 contrast is determined by the effective echo time of the T2Prep pulse, TEeff. TEeff is selected to differentiate MI and blood that share similar T1 values but have different T2 values. The T2Prep-IR preparation was incorporated into a fast gradient echo sequence to produce an image with both T1 and T2 weighting. Simulations predict that this method will generate improved contrast between MI and chamber blood compared to conventional IR methods. Comparisons between images acquired using conventional IR and T2Prep-IR in patients with MI indicate that this new approach significantly improves the blood-MI contrast (122+/-32% higher than that of IR with P<0.05). Our preliminary patient studies confirm that this preparation is helpful for improved delineation of subendocardial infarction.
18,972,338
Measurement of liver stiffness with two imaging techniques: magnetic resonance elastography and ultrasound elastometry.
To cross-validate the magnetic resonance elastography (MRE) technique with a clinical device, based on an ultrasound elastometry system called Fibroscan. Ten healthy subjects underwent an MRE and a Fibroscan test. The MRE technique used a round pneumatic driver at 60 Hz to generate shear waves inside the liver. An elastogram representing a map of the liver stiffness was generated allowing for the measurement of the average liver stiffness inside a region of interest. The Fibroscan technique used an ultrasound probe (3.5 MHz) composed of a vibrator that sent low-frequency (50 Hz) shear waves inside the right liver lobe. The probe acts as an emitter-receptor that measures the velocity of the waves propagated inside the liver tissue. The mean shear stiffness measured with the MRE and Fibroscan techniques were 1.95+/-0.06 kPa and 1.79+/-0.30 kPa, respectively. A higher standard deviation was found for the same subject with Fibroscan. This study shows why MRE should be investigated beyond the Fibroscan. The MRE technique provided elasticity of the entire liver, meanwhile the Fibroscan provided values of elasticity locally.
18,972,339
Consideration of physiological response in numerical models of temperature during MRI of the human head.
To examine the thermal effects of the physiological response to heating during exposure to radiofrequency (RF) electromagnetic fields in magnetic resonance imaging (MRI) with a head-specific volume coil. Numerical methods were used to calculate the temperature elevation in MRI of the human head within volume coils from 64-400 MHz at different power levels both with and without consideration of temperature-induced changes in rates of metabolism, perspiration, radiation, and perfusion. At the highest power levels currently allowed in MRI for head volume coils, there is little effect from the physiological response as predicted with existing methods. This study does not rule out the possibility that at higher power levels or in different types of coils (such as extremity or whole-body coils) the physiological response may have more significant effects. In modeling temperature increase during MRI of the human head in a head-sized volume coil at up to 3.0 W/kg head-average specific energy absorption rates, it may not be necessary to consider thermally induced changes in rates of metabolism, perfusion, perspiration, and radiation.
18,972,342
Cross-correlation delay to quantify myocardial dyssynchrony from phase contrast magnetic resonance (PCMR) velocity data.
To apply cross-correlation delay (XCD) analysis to myocardial phase contrast magnetic resonance (PCMR) tissue velocity data and to compare XCD to three established "time-to-peak" dyssynchrony parameters. Myocardial tissue velocity was acquired using PCMR in 10 healthy volunteers (negative controls) and 10 heart failure patients who met criteria for cardiac resynchronization therapy (positive controls). All dyssynchrony parameters were computed from PCMR velocity curves. Sensitivity, specificity, and receiver operator curve (ROC) analysis for separating positive and negative controls were computed for each dyssynchrony parameter. XCD had higher sensitivity (90%) and specificity (100%) for discriminating between normal and patient groups than any of the time-to-peak dyssynchrony parameters. ROC analysis showed that XCD was the best parameter for separating the positive and negative control groups. XCD is superior to time-to-peak dyssynchrony parameters for discriminating between subjects with and without dyssynchrony and may aid in the selection of patients for cardiac resynchronization therapy.
18,972,349
Assessment of histone acetylation levels in relation to cell cycle phase.
Histone acetylation affects chromatin structural organization, thus regulating gene expression and DNA-related cellular events. Levels of histone acetylation are tightly modulated in normal cells and frequently altered in tumors. Consequently, histone deacetylase inhibitors are currently being tested in clinical trials as anticancer drugs. Presented here is a protocol for measuring the degree of cellular histone tail acetylation, alone or in combination with DNA content to simultaneously evaluate cell ploidy and/or cell cycle progression. The procedure can also be employed to stain peripheral blood samples in order to assess mean histone acetylation levels in patients treated with histone deacetylase inhibitors.
18,972,367
Diphenyl diselenide protects against hematological and immunological alterations induced by mercury in mice.
Mercury is a heavy metal that can cause a variety of toxic effects on the organism, such as hematological and immunological alterations. In the present investigation, deleterious effects of mercury-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)(2) were studied. Male adult Swiss albino mice received daily a pretreatment with (PhSe)(2) (15.6 mg/kg, orally) for 1 week. After this week, mice received daily mercuric chloride (1 mg/kg, subcutaneously) for 2 weeks. A number of hematological (erythrocytes, leukocytes, platelets, hemoglobin, hematocrit, reticulocytes, and leukocytes differential) and immunological (immunoglobulin G and M plasma concentration) parameters were evaluated. Another biomarker of tissue damage, lactate dehydrogenase (LDH), was also determined. The results demonstrated that mercury exposure caused a reduction in the erythrocyte, hematocrit, hemoglobin, leukocyte, and platelet counts and an increase in the reticulocyte percentages. (PhSe)(2) was effective in protecting against the reduction in hematocrit, hemoglobin, and leukocyte levels. (PhSe)(2) ameliorated reticulocyte percentages increased by mercury. However, (PhSe)(2) was partially effective in preventing against the decrease in erythrocyte and platelet counts. Immunoglobulin G and M concentrations and LDH activity were increased by mercury exposure, and (PhSe)(2) was effective in protecting against these effects. In conclusion, (PhSe)(2) was effective in protecting against hematological and immunological alterations induced by mercury in mice.
18,972,395
Chronic alcohol consumption augments loss of sialic acid residues and alters erythrocyte membrane charge in type II diabetic patients.
In this study, the effects of alcohol consumption on erythrocyte membrane properties in type 2 diabetic patients were investigated. Therefore, we measured total and lipid-bound sialic acid (LSA) levels, sialidase activities, and erythrocyte membrane negative charge. Three groups, including control group (n = 20), alcohol-consuming diabetic patients group (n = 14), and diabetic patients without alcohol consumption group (n = 42), were created. Plasma total sialic acid (TSA) levels of the alcohol-consuming diabetic group were elevated as compared to the healthy control and diabetic group (p < 0.001 and p < 0.01, respectively). TSA levels of the diabetic group were significantly elevated as compared to the healthy control group (p > 0.001). Plasma LSA levels of the alcohol-consuming diabetic group were higher than that in the healthy control and diabetic group (p < 0.05 and p < 0.05, respectively). LSA levels of the diabetic group were found to be high as compared to the healthy control group (p < 0.05). Plasma sialidase activities of the alcohol-consuming diabetic group and diabetic group were significantly elevated as compared to the healthy control group (p < 0.05 and p < 0.05, respectively). Sialidase activities of the alcohol-consuming diabetic group were elevated as compared to the diabetic group, but this was not statistically significant (p > 0.05). Erythrocyte membrane negativity levels of the alcohol-consuming diabetic group and diabetic group were significantly decreased (p < 0.001 and p < 0.001, respectively) as compared to the healthy control group. Erythrocyte membrane negativity levels of the alcohol-consuming diabetic group were decreased as compared to the diabetic group, but this was not statistically significant (p > 0.05). In conclusion, our results indicate that chronic alcohol consumption may augment membrane alterations in type 2 diabetic patients.
18,972,396
Sputum eosinophil apoptotic rate is positively correlated to exhaled nitric oxide in children.
Exhaled nitric oxide (FE(NO)), a potential biomarker for asthma, is positively correlated with eosinophilic airway inflammation. Eosinophil apoptotic rate (AR) may be increased by NO but the relationship between eosinophil AR and NO has not been studied in vivo. This study tested the hypothesis that eosinophil AR will be positively related to FE(NO). Children with and without asthma were recruited and participated in an assessment that included FE(NO) measurement, skin prick reactivity, spirometry, and sputum induction. The absolute sputum eosinophil count and eosinophil AR were determined by morphology under light microscope after staining. There were 31 children recruited, mean age 11 years, 21 were asthmatic and 19 were boys. The median FE(NO) (range) was 15.6 parts per billion (3.1-102.6), 17 were atopic and the mean (SD)% FEV(1) was 85 (10)%. Sputum eosinophil AR was determined in 19 children (16 asthmatics), mean (SD) value 0.49 (0.13). There were positive relationships between eosinophil AR and FE(NO) (Spearman rho = 0.46, P = 0.046), eosinophil AR and % eosinophil count (Spearman rho = 0.45, P = 0.050) and also FE(NO) and % eosinophil count (Spearman rho = 0.49, P = 0.024). There is a positive relationship between FE(NO) and eosinophil AR. Nitric oxide may be involved in regulation of eosinophil AR in the airways.
18,972,415
Survival after surgical resection of pulmonary metastases and second primary squamous cell lung carcinomas in head and neck cancer.
Patients with head and neck squamous cell carcinoma (HNSCC) are at risk for developing both pulmonary metastasis and second primary lung cancer (SPLC). The objective of this study was to determine survival characteristics of patients with pulmonary lesions after curative treatment for HNSCC. Lung resection or biopsy specimens of 36 patients, curatively treated for HNSCC between 1978 and 2002, were defined as second primary squamous cell lung cancer or metastasis by loss of heterozygosity (LOH analysis). Twenty-two of them underwent surgical resection. Survival characteristics were estimated using Kaplan-Meier analysis according to the LOH characterization. The number of resected lung lesions ranged from 1 to 3. Median overall survival after lung surgery was 23.1 months for SPLC (n = 14) and 25.1 months for lung metastases (n = 8). Fourteen patients, SPLC (n = 6) and metastases (n = 8), did not undergo surgical resection, and their median overall survival was 3.7 and 4.4 months, respectively. Survival after resection of metachronic lung lesions following curative treatment of HNSSC is similar for lesions characterized as second primary squamous cell lung cancer and those characterized as metastases.
18,972,427
Analysis of 49 cases of flap compromise in 1310 free flaps for head and neck reconstruction.
The purpose of this study was to analyze the causes of flap compromise and failure in head and neck free flap reconstruction. We retrospectively reviewed 1310 free flap reconstructions for head and neck defects performed between July 1995 and June 2006. Forty-nine cases of flap compromise due to vascular obstruction (3.7%) were identified, and 27 flaps were lost (2%). Arterial occlusions occurred in 12 flaps, with a salvage rate of 33%. Eight flaps failed within the first 24 hours, and only 1 of these was salvageable. Five of the 8 flaps had intraoperative thrombosis due to technical difficulties. Venous occlusions occurred in 31 flaps, with a salvage rate of 58%. Twenty-two venous occlusions occurred within the first 72 hours. The main reason for venous failure was mechanical obstruction due to compression, twisting, kinking, or stretching of the vein. The most common cause of late failures (after 7 days) was unrecognized failure of a buried flap owing to the lack of reliable monitoring. Overall, there was no correlation between surgeon experience and flap failure, but the flap failure rate was lower in surgeons who had performed more than 70 free flap procedures. Precise surgical techniques, avoidance of mechanical obstruction, and better monitoring of buried flaps may further improve the success rate of free tissue transfer in complex head and neck reconstruction.
18,972,428
The stem cell niche of human livers: symmetry between development and regeneration.
Human livers contain two pluripotent progenitors: hepatic stem cells and hepatoblasts. The hepatic stem cells uniquely express the combination of epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), cytokeratin (CK) 19, albumin +/-, and are negative for alpha-fetoprotein (AFP). They are precursors to hepatoblasts, which differ from hepatic stem cells in size, morphology, and in expressing the combination of EpCAM, intercellular cell adhesion molecule (ICAM-1), CK19, albumin++, and AFP++. The hepatic stem cells are located in vivo in stem cell niches: the ductal plates in fetal and neonatal livers and canals of Hering in pediatric and adult livers. The hepatoblasts are contiguous to the niches, decline in numbers with age, wax and wane in numbers with injury responses, and are proposed to be the liver's transit-amplifying cells. In adult livers, intermediates between hepatic stem cells and hepatoblasts and between hepatoblasts and adult parenchyma are observed. Amplification of one or both pluripotent cell subpopulations can occur in diseases; for example, hepatic stem cell amplification occurs in mild forms of liver failure, and hepatoblast amplification occurs in forms of cirrhosis. Liver is, therefore, similar to other tissues in that regenerative processes in postnatal tissues parallel those occurring in development and involve populations of stem cells and progenitor cells that can be identified by anatomic, antigenic, and biochemical profiles.
18,972,441
Heme oxygenase-1 suppresses hepatitis C virus replication and increases resistance of hepatocytes to oxidant injury.
Oxidative injury to hepatocytes occurs as a result of hepatitis C virus (HCV) infection and replication. Modulation of host cell antioxidant enzymes such as heme oxygenase-1 (HO-1) may be useful therapeutically to minimize cellular injury, reduce viral replication, and attenuate liver disease. In this report, we evaluated the effects of HO-1 overexpression on HCV replication and hepatocellular injury. Full-length (FL) (Con1) or nonstructural (NS) replicons (I 389 NS3-3') were transfected with complete human HO-1 sequences or empty vector for control. Cell lines overexpressing HO-1 (twofold to sixfold above basal values) or empty vector were isolated, and their HCV RNA synthesis, pro-oxidant levels, and resistance to oxidative injury were assessed. HO-1 overexpression decreased HCV RNA replication in both FL and NS replicons without affecting cellular growth or DNA synthesis. The attenuation of HCV replication was significantly reversed in both replicon systems with HO-1 small interfering RNA (siRNA) knockdown. Both FL and NS replicons that overexpress HO-1 showed reduced prooxidant levels at baseline and increased resistance to oxidant-induced cytotoxicity. HO-1 induction with hemin also markedly decreased HCV replication in both parental FL and NS replicon cell lines. Conversely, knockdown of HO-1 messenger RNA (mRNA) by siRNA in parental FL or NS replicons did not significantly affect HCV replication, suggesting that less than basal levels of HO-1 had minimal effect on HCV replication. Overexpression or induction of HO-1 results in decreased HCV replication as well as protection from oxidative damage. These findings suggest a potential role for HO-1 in antiviral therapy and therapeutic protection against hepatocellular injury in HCV infection.
18,972,446
Oxidation leading to reduction: redox-induced electron transfer (RIET).
Complex electron transfer reactions have been characterized whereby in addition to electron transfer, subsequent electrochemical, chemical and even in some cases biological consequences occur. These include a secondary electron transfer that leads to a major rearrangement of the electronic structure, such that an initial oxidation leads to a reduction (or an initial reduction leads to an oxidation) for these valence ambiguous compounds. Mixed valency and valence-tautomeric behaviors can additionally result from these complex electron-transfer-induced reactions.
18,972,460
A novel Ni(4) complex exhibiting microsecond quantum tunneling of the magnetization.
A highly asymmetric Ni(II) cluster [Ni(4)(OH)(OMe)(3)(Hphpz)(4)(MeOH)(3)](MeOH) (1) (H(2)phpz=3-methyl-5-(2-hydroxyphenyl)pyrazole) has been prepared and its structure determined by means of single-crystal X-ray diffraction by using synchrotron radiation. Variable-temperature bulk-magnetization measurements show that the complex exhibits intramolecular-ferromagnetic interactions leading to a spin ground state S=4 with close-lying excited states. Magnetization and high-frequency EPR measurements suggest the presence of sizable Ising-type magnetic anisotropy, with zero-field splitting parameters D=-0.263 cm(-1) and E=0.04 cm(-1) for the spin ground state, and an isotropic g value of 2.25. The presence of both axial and transverse anisotropy was confirmed through low-temperature specific heat determinations down to 300 mK, but no slow relaxation of the magnetization was observed by AC measurements down to 1.8 K. Interestingly, AC susceptibility measurements down to temperatures as low as 23 mK showed no indication of slow relaxation of the magnetization in 1. Thus, despite the presence of an anisotropy barrier (U approximately 4.21 cm(-1) for the purely axial limit), the magnetization relaxation remains extremely fast down to the lowest temperatures. The estimated quantum tunneling rate, Gamma>0.667 MHz, makes this complex a prime candidate for observation of coherent tunneling of the magnetization.
18,972,463
Cyclic peptides from Oldenlandia affinis DC. Molecular and biological properties.
A new isolation procedure for Kalata polypeptides from the tropical plant Oldenlandia affinis DC is described. Fractions were screened by thin-layer chromatography, and Van Urk positive fractions were tested for oxytocic activity in estrogenized rat uteri. By using this procedure, we were able to isolate and characterize three macrocyclic polypeptides with uterine activity. Their amino acid sequence and biological effects have been analyzed, and their NMR spectra were compared with those of the earlier ones. All three peptides showed hemolytic activity on human blood, and were tested for antibiotic effect against E. coli, Staphylococcus aureus, and Hemophilus influenzae.
18,972,522
Evaluation of the utility of neutral-loss-dependent MS3 strategies in large-scale phosphorylation analysis.
Phosphopeptide identification and site determination are major challenges in biomedical MS. Both are affected by frequent and often overwhelming losses of phosphoric acid in ion trap CID fragmentation spectra. These losses are thought to translate into reduced intensities of sequence informative ions and a general decline in the quality of MS/MS spectra. To address this issue, several methods have been proposed, which rely on extended fragmentation schemes including collecting MS3 scans from neutral loss-containing ions and multi-stage activation to further fragment these same ions. Here, we have evaluated the utility of these methods in the context of a large-scale phosphopeptide analysis strategy with current instrumentation capable of accurate precursor mass determination. Remarkably, we found that MS3-based schemes did not increase the overall number of confidently identified peptides and had only limited value in site localization. We conclude that the collection of MS3 or pseudo-MS3 scans in large-scale proteomics studies is not worthwhile when high-mass accuracy instrumentation is used.
18,972,524
Modelling the sulfoxygenation activity of vanadate-dependent peroxidases.
Vanadate-dependent peroxidases contain, in their active center, vanadate covalently attached to histidine in an overall trigonal-bipyramidal array. We describe here the synthesis and characterization of optically active amino alcohols and their vanadium(V) complexes, and we show that the structural models of the active center thus obtained are also functional models for the sulfide-peroxidase activity of the enzyme in heterogeneous catalysis. The heterogeneous systems were obtained by immobilizing the complexes on silica gel and mesoporous silicas, and by aggregation. The following ligands, ligand precursors, and V compounds have been structurally characterized: (R)-(2-phenylethanol)-(R)-1-phenylethylamine (HL(A)), (R,R)-bis[2-phenyl(ethylmethylether)]ammonium chloride ([L(D)]+Cl(-)), the carbasilatranes (R,R)-methoxy{N,N',N''-2,2',3-[bis(1-phenylethanolato)propyl]amino}silane ((R,R)-Si(OMe)L(E)), (R,R)-methoxy-{N,N',N''-1,2',3-[(1-phenylethanolato)-(2-phenylethanolato)propyl]amino}silane ((R,R)-Si(OMe)L(E')), and [VO(L(F))(OSiMe2(t)Bu)], where H2L(F)=ethylbis(2-hydroxy-2-phenylethyl)amine.
18,972,532
Proteome approaches combined with Fourier transform infrared spectroscopy revealed a distinctive biofilm physiology in Bordetella pertussis.
Proteome analysis was combined with whole-cell metabolic fingerprinting to gain insight into the physiology of mature biofilm in Bordetella pertussis, the agent responsible for whooping cough. Recent reports indicate that B. pertussis adopts a sessile biofilm as a strategy to persistently colonize the human host. However, since research in the past mainly focused on the planktonic lifestyle of B. pertussis, knowledge on biofilm formation of this important human pathogen is still limited. Comparative studies were carried out by combining 2-DE and Fourier transform infrared (FT-IR) spectroscopy with multivariate statistical methods. These complementary approaches demonstrated that biofilm development has a distinctive impact on B. pertussis physiology. Results from MALDI-TOF/MS identification of proteins together with results from FT-IR spectroscopy revealed the biosynthesis of a putative acidic-type polysaccharide polymer as the most distinctive trait of B. pertussis life in a biofilm. Additionally, expression of proteins known to be involved in cellular regulatory circuits, cell attachment and virulence was altered in sessile cells, which strongly suggests a significant impact of biofilm development on B. pertussis pathogenesis. In summary, our work showed that the combination of proteomics and FT-IR spectroscopy with multivariate statistical analysis provides a powerful tool to gain further insight into bacterial lifestyles.
18,972,542
Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.
Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.
18,972,553
Inhibition of Kupffer cell-mediated early proinflammatory response with carbon monoxide in transplant-induced hepatic ischemia/reperfusion injury in rats.
Proinflammatory responses play critical roles in hepatic ischemia/reperfusion (I/R) injury associating with liver transplantation (LTx), and carbon monoxide (CO) can effectively down-regulate them. Using wild-type (WT) to enhanced green fluorescent protein (EGFP)-transgenic rat LTx with 18-hour cold preservation in University of Wisconsin solution, this study analyzed the relative contribution of donor and host cells during early posttransplantation period and elucidated the mechanism of hepatic protection by CO. CO inhibited hepatic I/R injury and reduced peak alanine aminotransferase levels at 24 hours and hepatic necrosis at 48 hours. Abundant EGFP(+) host cells were found in untreated WT liver grafts at 1 hour and included nucleated CD45(+) leukocytes (myeloid, T, B, and natural killer cells) and EGFP(+) platelet-like depositions in the sinusoids. However, reverse transcription polymerase chain reaction (RT-PCR) analysis of isolated graft nonparenchymal cells (NPCs) revealed that I/R injury-induced proinflammatory mediators [for example, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS)] were not up-regulated in purified CD45(+) cells of donor or host origin. Instead, TNF-alpha and IL-6 messenger RNA (mRNA) elevation was exclusively seen in isolated CD68(+) cells, whereas iNOS mRNA up-regulation was seen in hepatocytes. Nearly all CD68(+) cells at 1 hour after LTx were EGFP(-) donor Kupffer cells, and CO efficiently inhibited TNF-alpha and IL-6 up-regulation in the CD68(+) Kupffer cell fraction. When graft Kupffer cells were inactivated with gadolinium chloride, activation of inflammatory mediators in liver grafts was significantly inhibited. Furthermore, in vitro rat primary Kupffer cell culture also showed significant down-regulation of lipopolysaccharide (LPS)-induced inflammatory responses by CO. These results indicate that CO ameliorates hepatic I/R injury by down-regulating graft Kupffer cells in early postreperfusion period. The study also suggests that different cell populations play diverse roles by up-regulating distinctive sets of mediators in the acute phase of hepatic I/R injury.
18,972,563
Degeneration of acetabular articular cartilage to bipolar hemiarthroplasty.
This study examined the rate of degeneration of acetabular cartilage by the bipolar head according to time, and also which clinical factors are related to the degeneration of acetabular cartilage. Among 192 patients (226 hip joints) who received bipolar hemiarthroplasty from August 1996 to August 2002, 61 patients (65 hip joints) were enrolled in this study, who were followed up for more than 2 years and showed no signs of dislocation, infection, or functional problems. A modified form of a computer assisted vector wear analysis program was used to measure the rate of degeneration of the acetabular cartilage. The factors that appeared to affect the rate of acetabular degeneration in the two groups was evaluated. The average linear degenerative change in the acetabular cartilage and the volumetric degenerative change were 0.23 +/- 0.107mm/year and 114 +/- 47.2mm3/year, respectively. The result showed significant differences in activity and HHS between the 2 groups. The HHS showed a reverse relationship with the linear degeneration and volumetric degeneration, and the activity showed a correlation with the linear and volumetric degeneration. The acetabular cartilage degenerates faster as the patient' activity increases, and slower with a higher HHS. When surgeons perform hip joint arthroplasty, it is strongly recommended that the life expectancy and the level of activity should be considered when deciding between a hemiarthroplasty and total hip arthroplasty.
18,972,591
Severe paradoxical reaction requiring tracheostomy in a human immunodeficiency virus (HIV)-negative patient with cervical lymph node tuberculosis.
During drug treatment of tuberculous lymphadenitis, paradoxical response (PR) may occasionally occur. Continued treatment or lymph node aspiration improves PR without severe sequelae. However, we report a case of severe PR in a patient with cervical lymph node tuberculosis causing airway obstruction due to retropharyngeal lymph node swelling during antituberculous treatment. Tracheostomy and drainage of the node were performed to secure the airway. Possible airway obstruction due to PR must be suspected when cervical lymph node tuberculosis involves the retropharyngeal lymph node.
18,972,608
Laparoscopic enucleation of a nonfunctioning neuroendocrine tumor of the pancreas.
Laparoscopic approaches are increasingly used in pancreatic surgery. In the treatment of neuroendocrine tumors (NETs) of the pancreas, enucleation is one of the recommended surgery. Although many clinical experiences have reported the safety and efficacy of laparoscopic enucleation of functioning NETs, such as insulinomas, few reports have explored such treatment for non-functioning NETs. Here, we present a case of 70-year old female patient who underwent successful laparoscopic enucleation of a nonfunctioning NET located in the body of the pancreas.
18,972,611
Nerve plexus invasion in pancreatic cancer: spread patterns on histopathologic and embryological analyses.
Although extrapancreatic nerve plexus (PLX) invasion is an important prognostic factor in pancreatic carcinoma, the spreading patterns of carcinoma via PLX have not been carefully explored because of the complex anatomical structures around the pancreas. Fifty-eight patients underwent pancreaticoduodenectomy for carcinoma of the head of the pancreas. The patterns of PLX invasion were evaluated by careful pathological examination. The relationship between tumor location considering the embryological structure of the pancreas and the site of PLX invasion was investigated with an immunohistochemical study using pancreatic polypeptide. Forty-six patients (79%) had PLX invasion. The typical patterns of PLX invasion were detected by pathological examination. Patients with carcinoma in ventral pancreas frequently had pancreatic head plexus 1, pancreatic head plexus 2, and superior mesenteric arterial plexus invasion. Patients with carcinoma in dorsal pancreas had invasion into common hepatic artery plexus and plexus within the hepatoduodenal ligament. A significant correlation between tumor location and the site of PLX invasion was observed. Extrapancreatic nerve plexus invasion by carcinoma of the head of the pancreas could be divided into 2 patterns based on an embryological structure of the pancreas and the location of the tumor. These results about PLX invasion may provide important information to determine surgical strategy for carcinoma of the head of the pancreas.
18,972,625
Cardiogenic shock complicating myocardial infarction and outcome following percutaneous coronary intervention.
Cardiogenic shock is the commonest cause of death in acute myocardial infarction (AMI). Although the syndrome of cardiogenic shock complicating AMI is common to all, the spectrum of underlying pathology is broad. While thrombolysis can be attempted with inotropic support or augmentation of blood pressure with an intra-aortic balloon pump, the greatest mortality benefit is seen after urgent coronary angiography and early revascularization. The long-term SHOCK Trial six-year follow-up results confirm durability of early revascularization over medical stabilization in shock patients. Indeed, cardiogenic shock is a catheter laboratory emergency. Percutaneous left ventricular assist devices may provide an advance in the management of patients with left ventricular dysfunction and cardiogenic shock.
18,972,627
Changes in nutritive value of fish, Channa punctatus after chronic exposure to zinc.
The present investigation was undertaken to assess the effects of sublethal concentrations of zinc (0.1 and 0.2 mgl(-1)) on the nutritional value of fish Channa punctatus after exposure for 135 days. The parameters studied were, levels of total proteins, glycogen, total lipids, cholesterol and vitamins (A and D) in the muscle. Total proteins, glycogen, total lipids and vitamin D show highly significant decline from day 90 to 135, while cholesterol and vitamin A, show no significant changes upto 105 days. This study signifies a drastic reduction in the nutritive value of fish, which is compounded by the fact that under natural conditions fish are exposed to these levels of zinc for prolonged periods.
18,972,681
Histopathological alterations of Nile tilapia, Oreochromis niloticus in acute and subchronic alachlor exposure.
Histopathological alterations in Nile tilapia, Oreochromis niloticus, aged 3 months and subjected to acute and subchronic alachlor exposure were studied by light microscopy LC50 values of alachlor for 24 hr 48 hr, 72 hr and 96 hr were 963.6, 563, 448, and 381.9 microg l(-1), respectively and the maximum acceptable toxicant concentration (MATC) was 350 microg l(-1). Fish were exposed to 381.9 (acute) and 35 microg l(-1) (sub-chronic) of alachlor for 24, 48, 72 and 96 hr and 90 days, respectively Gill lamellae and kidney tubules were the primary target organs for the acute toxic effect of alachlor while in the subchronic exposure, the toxic effect on the gills was less marked than that of the kidneys and liver Gill alterations included edema of the epithelial cell system, aneurisms with some ruptures, hypertrophy and hyperplasia of epithelial cells. The liver showed hydropic swelling of hepatocytes and vacuolation. Lipid vacuoles were observed in hepatocytes in the second and third month of subchronic exposure. The kidney showed hydropic swelling of tubular cells, lipid vacuole accumulation in many tubules, and nuclear pyknosis. The findings of this study could be used as a guideline forbiomonitoring programs on populations of Nile tilapia cultured near alachlor contaminated areas.
18,972,686
Study of bio-physico-chemical parameters of Mothronwala swamp, Dehradun (Uttarakhand).
Aquatic biodiversity is one of the most essential characteristics of the aquatic ecosystem formaintaining its stability and a means of coping with any environmental change. The entire stretch of the Mothronwala swamp has rich riparian vegetation for providing conducive environment for the growth of aquatic organisms. The present work has been undertaken to study the bio-physico-chemical characteristics of the swamp. The data on physico-chemical environmental variables (temperature, total dissolved solutes, size and composition of substratum, pH, dissolved oxygen, alkalinity chlorides, and hardness) have been given under the present contribution. A total of 16 genera of aquatic insects belonging to orders Trichoptera, Coleoptera, Hemiptera, Ephemeroptera, Odonata and Phylum Mollusca represented the macroinvertebrates of Mothronwala swamp. The fresh water swamp of Mothronwala is under threat due to human interference and other anthropogenic activities. Some of the natural and anthropogenic environmental problems of the Mothronwala swamp have been identified and the ameliorative measures for the protection of aquatic environment and the conservation measures for the swamp have been suggested. The qualitative study revealed the present status of the aquatic biodiversity of the swamp and also about the physico-chemical parameters, which would be very helpful for policy makers to take precautionary measures to save the swamp.
18,972,696
Infant mortality statistics from the 2005 period linked birth/infant death data set.
This report presents 2005 period infant mortality statistics from the linked birth/infant death data file by a variety of maternal and infant characteristics. The linked file differs from the mortality file, which is based entirely on death certificate data. Descriptive tabulations of data are presented and interpreted. Excluding rates by cause of death, the infant mortality rate is now published with two decimal places. The U.S. infant mortality rate was 6.86 infant deaths per 1,000 live births in 2005, which is statistically unchanged from 6.78 in 2004. Infant mortality rates ranged from 4.89 deaths per 1,000 live births for Asian or Pacific Islander (API) mothers to 13.63 for non-Hispanic black mothers. Among Hispanics, rates ranged from 4.42 for Cuban mothers to 8.30 for Puerto Rican mothers. Infant mortality rates were higher for infants who were born in multiple deliveries or whose mothers were born in the 50 states and the District of Columbia or were unmarried. Infant mortality was also higher for male infants and infants born preterm or at low birthweight. The neonatal mortality rate was essentially unchanged from 2004 (4.52) to 2005 (4.54). The postneonatal mortality rate increased 3 percent from 2.25 in 2004 to 2.32 in 2005. Infants born at the lowest gestational ages and birthweights have a large impact on overall U.S. infant mortality. For example, more than one-half (55 percent) of all infant deaths in the United States in 2005 occurred to the 2 percent of infants born very preterm (less than 32 weeks of gestation). Infant mortality rates for late preterm infants (34-36 weeks of gestation) were three times those for term infants (37-41 weeks). The three leading causes of infant death--congenital malformations, low birthweight, and sudden infant death syndrome (SIDS)--accounted for 44 percent all infant deaths. The percentage of infant deaths that were "preterm-related" increased from 34.6 percent in 2000 to 36.5 percent in 2005. The preterm-related infant mortality rate for non-Hispanic black mothers was 3.4 times higher and the rate for Puerto Rican mothers was 87 percent higher than the rate for non-Hispanic white mothers.
18,972,721
U.S. decennial life tables for 1999-2001, United States life tables.
This report presents period life tables for the United States based on age-specific death rates for the period 1999-2001. These tables are the most recent in a 100-year series of decennial life tables for the United States. This report presents complete life tables by age, race (white and black), and sex. Also presented are standard errors of the probability of dying and life expectancy. The data used to prepare these life tables are population estimates based on the 2000 decennial census, deaths occurring in the United States to U.S. residents in the 3 years 1999-2001, counts of U.S. resident births in the years 1997-2001, and population and death counts from the Medicare program for years 1999-2001. In 1999-2001, life expectancy at birth was 76.83 years for the total U.S. population, representing an increase of 27.59 years from a life expectancy of 49.24 years in 1900. Between 1900 and 2000, life expectancy increased by 40.08 years for black females (from 35.04 to 75.12), by 35.54 years for black males (from 32.54 to 68.08), by 28.89 years for white females (from 51.08 to 79.97), and by 26.51 years for white males (from 48.23 to 74.74).
18,972,722
[Effects of electroacupuncture at points "Weibingfang" on EGF and EGFR mRNA expressions in rats with lesion of gastric mucosa].
To probe the mechanism of electroacupuncture at points "Weibingfang" in treatment of acute gastric mucosal lesion. Forty Wistar rats of sanitary degree were randomly divided into 4 groups, normal group, model group, sham-model group and Weibingfang group, 10 rats in each group. The acute gastric mucosal lesion model was made by intragastric perfusion of anhydrous alcohol. The Weibingfang group were treated by electroacupuncture at "Neiguan" (PC 6), "Zhongwan" (CV 12) and "Zusanli" (ST 36) with sparse-dense wave, frequency of 10-30 Hz, current intensity of 2 mA, for 20 min. One hour after the treatment, the blood from the abdominal aorta and the gastric mucosa tissue were taken, and serum epidermal growth factor (EGF) level and epidermic growth factor receptor mRNA (EGFR mRNA) expression in the gastric mucosa were detected with enzyme linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) respectively. There were significant differences in blood EGF level (41.62 +/- 12.58) ng/L and EGFR mRNA expression (0.78 +/- 0.03) in the model group were significantly different from [(60.37 +/- 12.01) ng/L and 0.55 +/- 0.04] in the normal group and [(61.21 +/- 13.46) ng/L and 0.53 +/- 0.05] in the sham-model group (P < 0.05); after electroacupuncture, blood EGF level (70.59 +/- 10.14) ng/L increased and the EGFR mRNA expression (1.18 +/- 0.02) in the gastric mucosa was up-regulated with a significant differences as compared with those in the model group (P < 0.05). Point "Weibingfang" can promote proliferation, differentiation and migration of the gastric mucosal epidermic cells to repair the gastric mucosal lesion.
18,972,736
[A hypothesis about component model of substances of channels and collaterals].
The theory of channels and collaterals is a very important "substance" prop for the basic theories of TCM. After component model of substances of channels and collaterals is raised, according to the principle, structure and function are dialectical unity, the author finds in deeply research on a great number of completed experimental investigations of corresponding anatomic position of channels and collaterals and similar physiology at home and abroad that the difficult to understand TCM concepts such as "interdependence between yin and yang", "defensive energy" all could be displayed by the substance of body liquid showing liquid crystalline state during living of channels and collaterals.
18,972,738
Gene-environment interaction and the metabolic syndrome.
The metabolic syndrome, which has been shown to affect as many as 20% of the general adult US population, is generally described as a cluster of cardiovascular risks factors, most notably obesity, type 2 diabetes or resistance to insulin-stimulated glucose uptake (insulin resistance), dyslipidaemia and hypertension. All these risk factors are under both genetic and environmental control; they are considered individually as complex genetic diseases. Prior to pharmacological interventions for hypertension, diabetes and dyslipidaemia, lifestyle changes, in particular weight loss (or weight maintenance) and physical activity, were prioritized and constituted an effective first-line intervention strategy. Here we want to focus on three clinical components of the metabolic syndrome and the environmental factors that are considered to be the most significant targets for primary interventions: type 2 diabetes and exercise, obesity and diet, and hypertension and salt. Our experimental approach is to go from candidate gene strategy to genome-wide association. The identification of the genetic component of these risk factors is a major challenge, and it is hoped that this would help unravel mechanistic pathways that can ultimately serve as new targets for therapeutic intervention.
18,972,748
Unbiased forward genetics and systems biology approaches to understanding how gene-environment interactions work to predict susceptibility and outcomes of infections.
Like most human diseases, infectious diseases are effected by complex genetic traits and multiple, interactive environmental and inherent host factors. By linking specific genotypes to disease susceptibility phenotypes we can identify the genetic basis for inter-individual differences in disease susceptibility as well as gain insight into how gene-environment interactions influence infection outcomes. Our research has focused on delineating interactive pathways and molecular events modulating host resistance or susceptibility to specific pathogens. Our model system has been that of Group A Streptococcus infections that can manifest in starkly different ways and cause distinct diseases in genetically distinct individuals. We have extended our work to other pathogens, including those with a potential of causing major, global biological threats. In as much as it is quite difficult to conduct certain infectious disease studies in humans, there has been a critical need for small animal models for infectious diseases. Appreciating the limitations of existing models, we developed several novel and complementary mouse models that are ideal for use in systems genetics studies of complex diseases. These models not only allow biological validation of known genetic associations, but importantly they afford an unbiased tool for discovering novel genes and pathways contributing to disease outcomes, under different environments.
18,972,751
Effect of additive metals, Sn, Ga, and In in Ag-Pd-Au-Cu alloys on initial bond strength of 4-META adhesive cement to these alloys.
The purpose of this study was to investigate the effects of three additives, Sn, Ga, and In, as well as the main constituents, Pd and Cu, of Ag-Pd-Au-Cu alloys on the initial bond strength of 4-META adhesive cement to these alloys. The Ag-Pd-Au-Cu alloys consisted of 20%, 30% or 40% Pd, and 10%, 15% or 20% Cu, 20% Au, and Ag as balance. Besides, additive metals (Sn, Ga, and In) of 2% and 4% were added to these compositions. The addition of three additives, in general, increased the initial bond strength of the cement in comparison to the mother compositions (0% additives), although the degrees of effectiveness of the three additives were different and varied with their contents. Among these additives, a remarkable increase in bond strength was observed with the addition of In. The increase in Cu content, in many cases, resulted in an increase in bond strength at high Pd contents (30% and 40%), but a decrease at low Pd content (20%) in some cases. The positive effects of the three additives and Cu could be due to the formation of a suitable oxide layer for strong bonding with 4-META.
18,972,784
Chemical constituents and pharmacological properties of Radix Inulae.
Radix Inulae is used as a gastric and antibacterial agent in traditional Chinese and Tibetan medicines. Most of its chemical constituents have been identified and include a series of sesquiterpenes with various carbon skeletons such as: eudesmanolide, elemanolide, germacranolide, sesquicaranolide, guaianolide and humulane. Certain organic solvent fractions and sesquiterpenes from Radix Inulae have been found to significantly inhibit the growth of tumor cell strains in vitro. They also show antibacterial, cardiovascular and hypoglycaemic as well as insulin-sensitization activities. The present review summarizes research on the chemistry and biological activity of Radix Inulae.
18,972,829
Histone deacetylase inhibitors from the rhizomes of Zingiber zerumbet.
Histone acetylation and deacetylation play fundamental roles in the modulation of chromatin topology and the regulation of gene transcription. Histone deacetylase (HDAC) inhibitors that inhibit proliferation and induce differentiation and/or apoptosis of tumor cells in culture and in animal models have been identified. A number of structurally diverse histone deacetylase inhibitors have shown potent antitumor efficacy with little toxicity in vivo in animal models. In the context of our natural product chemistry program dealing with the development of new potent anticancer agents, we have examined the isolation from Zingiber zerumbet as leads for novel HDAC inhibitors. Zingiber zerumbet (L.) J. E. Smith (Zingiberaceae) is a wild ginger that typically grows widely in Southeast Asia. Isolation of the n-hexane soluble fraction from Zingiber zerumbet yielded two major sesequiterpenoids, 6-methoxy-2E,9E-humuladien-8-one (1) and zerumbone (2). The structures were elucidated on the basis of spectroscopic data. The histone deacetylase (HDAC) activities of compounds 1 and 2 were determined in vitro against HDAC enzyme assay. Compound 1 exhibited growth inhibitory activity on six human tumor cell lines, and showed potential inhibitory activity in histone deacetylase (HDAC) enzyme assay (GI50 = 1.25 microM). It also exhibited growth inhibitory activity on five human tumor cell lines and more sensitive inhibitory activity on the MDA-MB-231 breast tumor cell line (IC50 = 1.45 microM). Further structure-activity relationships of position C-6 and C-7 from aromatic ring will be reported in due course.
18,972,844
Management of infants and young children with fever without source.
There is considerable variation in the clinical management of infants and children with FWS. Community pediatricians generally do not follow clinical practice guidelines that are taught and used at academic training institutions. These guidelines are presented in Sidebar 1 (see page 677) and Sidebar 2. In general, the guidelines provided that all febrile neonates (>38.0 degrees C) should have a "full sepsis evaluation", including lumbar puncture, and be admitted for parenteral antibiotic therapy. Non-toxic appearing infants 29-90 days of age with FWS >38.0 degrees C can be managed using low risk laboratory and clinical criteria. Non-toxic appearing infants >90 days of age who have received Hib and PCV-7 vaccines are at low risk for occult bacteremia and meningitis. Therefore, the only laboratory tests necessary in this age group with FWS >39.0 degrees C are a urinalysis and urine culture for circumcised males <6 months of age and uncircumcised males and females <24 months of age.
18,972,849
Effectiveness of intravenous bisphosphonate in treatment of giant cell tumor: a case report and review of the literature.
Giant cell tumor is a benign locally aggressive tumor. The standard treatment is en bloc resection followed by major reconstructive surgery, or extended curettage conjunction with bone grafting or the use of bone cement implantations. Surgical treatment of giant cell tumor at the sacrum is associated with high morbidity, and local recurrence. The authors present a case of giant cell tumor at the sacrum treated with intravenous 4 mg zoledronate every 4 weeks for seven courses followed with curettage and cement implantation. At two years follow-up, the patient had no pain, no neurological deficit, and no local recurrence. The patient's gait was normal. From the present study, the authors demonstrate the effectiveness of zoledronate for treatment of giant cell tumor at the sacrum. It can reduce the morbidity from major surgery.
18,972,907
[Voiding symptoms as presentation of an intravesical foreign body].
The presence of intravesical foreign bodies is exceptional; it is not a common emergency. Most foreign bodies have a sexual-erotic origin, although we cannot forget others such as elements left by the surgeon in the surgical field. We performed a bibliographic review on the topic. We performed a PubMed (MEDLINE) electronic bibliographic search with the mesh terms "foreign-body migration" [MESH] AND "Urinary Bladder" [MESH] and bibliographic citations. We performed a bibliographic review establishing a classification depending on the origin and diagnosis, as well as treatment. Most publications are case reports. We described the most frequent presentation which was the same than we have in our Center. We found a total of 122 works, nine of which were reviews; we selected 20 works. Although most are case reports, the reviews establish a classification depending on the origin: so, they refer to those foreign bodies directly introduced into the bladder: 1. By the patient: hairpins, safety pins, pencils, copper wires, hairs; 2. Accidentally: bullets; 3. Iatrogenic: fragments of bladder or ureteral catheters, staples, sutures. Foreign bodies migrated from other places: urological, gynecological, gastrointestinal, or vascular origin. We established a diagnostic and therapeutic algorithm. Bladder foreign bodies are not as frequent as it is believed. Most are found incidentally. Lower urinary tract symptoms are the most frequent, as the antecedent of manipulation by the patient or others in the genital-urologic sphere. The treatment of choice is extraction using the least invasive and most simple method for the patient.
18,972,912
[Nonspecific sexual cord testicular tumor. Case report].
We report one case of gonadal stromal testicular tumor and perform a bibliographic review. We present the case of a 42 year-old male patient consulting for a painless right testicular mass. Orchiectomy was performed and the patient underwent follow-up. Nonspecific sexual cord tumors are extremely rare, with slow growing and benign behaviour, presenting positive staining for various markers.
18,972,920
The racial geography of child welfare: toward a new research paradigm.
This article examines the community-level impact of concentrated child welfare agency involvement in African American neighborhoods. Based on interviews of 25 African American women in a Chicago neighborhood, the study found that residents were aware of intense agency involvement in their neighborhood and identified profound effects on social relationships including interference with parental authority, damage to children's ability to form social relationships, and distrust among neighbors. The study also discovered a tension between respondents' identification of adverse consequences of concentrated state supervision for family and community relationships and neighborhood reliance on agency involvement for needed financial support. The author discusses the implications of these findings for a new research paradigm aimed at understanding the community-level effects of racial disproportionality.
18,972,935
Addressing the disproportionate representation of children of color: a collaborative community approach.
The state of Indiana recommended a committee be formed to address the disproportional representation of black youth in out-of-home placements. In response, the Indiana Disproportionality Committee (IDC) was established. This article presents the development, objectives and future of the IDC. One of the objectives, research, will be offered as an example of the committee's collaborative strategies. The IDC, in partnership with another organization, has begun exploring relationships between ethnicity, risk factors and treatment outcomes. The results of this research effort have examined disproportion and disparity, leading the IDC to identify needs for change within the state. Barriers and successes of the IDC will be shared, so that others can use these efforts to guide their own strategies to reduce disproportionality.
18,972,942
Two years into the storm over pricing to and collecting from the uninsured--a hospital valuation expert examines the risk/return dynamics and asks: would fair pricing and fair medical debt repayment plans increase yields to hospitals and simultaneously mitigate these controversies?
As the controversies over 501(c)(3) "charitable" hospitals' pricing, collections, and charity care practices that emerged in the winter and spring of 2003 continue unabated--now involving government officials from city councils and county boards to state attorneys general and Congress as well as numerous class action lawsuits--a hospital valuation expert and risk analyst looks at the fundamental economic and strategic issues, concluding that the risk/return dynamics are out of whack in that hospitals are facing mushrooming, multifaceted troubles over what has been a very low net yield patient population. After interviewing patient account representatives at hospitals and conducting other research, this analyst asks: Should attention have been focused at the national and state hospital association levels in 2003 to take steps to increase the net yield to hospitals from the uninsured population through more equitable pricing and better medical debt repayment terms, steps that might have mitigated these controversies? Many hospitals and hospital associations have been so intent on proving hospitals' legal right to charge "list price" to and sue the uninsured that they have overlooked a simple yet effective business premise that many hospital patient accounts representatives already fully know: Fair pricing and fair payment terms are actually good business. The author asserts that the controversies that emerged in 2003 actually represented a significant opportunity that, with a different approach, would likely have resulted in hospitals being able to collect significantly more money from the uninsured population while, at the same time, lessening or even avoiding the destructive ramifications that have occurred in the form of investigations, legislation, and lawsuits. To realize higher net yields from the uninsured, highly specific leadership steps need to be taken uniquely at national and state "association" levels in order to avoid the negative financial consequences of fragmented actions that can cause individual hospitals to become "magnets" for the uninsured. Steps at the individual hospital level need to be preceded by coordinated leadership at the "association" level if these difficult controversies are to be transformed into an opportunity for more revenue from the uninsured, an opportunity that existed in 2003 and before.
18,972,978
Financial effects of an influenza pandemic on US hospitals.
We estimate the financial effects of an influenza pandemic on US hospitals, including the cost of deferring elective admissions and the cost of uncompensated care for uninsured patients. Using US pandemic planning assumptions and national data on health care costs and revenues, a 1918-like pandemic would cause US hospitals to absorb a net loss of $3.9 billion, or an average $784,592 per hospital. Policymakers should consider contingencies to ensure that hospitals do not become insolvent as a result of a severe pandemic.
18,972,986
Leasing vs. owning a medical office: an analytical model.
Physicians often face a major financial dilemma: To lease or own their medical office. This article takes a set of typical assumptions for a real estate market and analyzes the capital costs, cash flow, and investment implications of the option of leasing a medical office versus owning a similar property. The paper analyzes the financial aspects of each option and the impact on net physician income and potential return-on-investment. A model for analysis is presented that can be used by practitioners who advise physicians in such decision-making.
18,972,995
The impact of HMO and hospital competition on hospital costs.
This study examines the impact of HMO penetration and competition on health system performance, as measured by hospital cost per adjusted admissions. The study population consisted of acute-care hospitals in the United States. The findings of this study suggest that there is no relationship between HMO competition and hospital cost per adjusted admission. Governmental efforts to stimulate competition in the hospital market, if focused on promoting HMOs, are not likely to produce cost-containing results quickly.
18,973,002
[Effects of Forskolin on proliferation cell-cycle distribution and activation of the murine T lymphocytes in vitro].
To investigate the effects of Forskolin on activation, proliferation, and cell-cycle distribution of murine CD3+ T lymphocytes, and study the mechanisms of its immunosuppressive effect. Singel cell suspensions were prepared from murine lymph nodes. Fluorescence conjugated monoclonal antibodies and flow cytometry were used to detect the expression of CD69 activated by Con A, the proliferation index of activated mouse T lymphocytes was analyzed by CFDA-SE staining, the distribution of the cell cycle was analyzed by PI staining. Forskolin (10(-7), 10(-6), 10(-5) M) could inhibit both the expression of CD69 on CD3+ T lymphocytes and T lymphocyte proliferation index stimulated by Con A in a dose-dependent manner. The C0/G1 of T lymphocytes increased but the S, G2/M phase decreased. Forskolin can inhibit the activation and proliferation of murine T lymphocytes in vitro, and arrest activated T lymphocytes from G0/G1 to S or G2/M. Forskolin is a potential immunosupressive agent.
18,973,017
[Study on self-microemulsifying drug delivery system of Jiaotai Pill active components].
To develop self-microemulsifying drug delivery system (SMEDDS) of Jiaotai Pill active components and its quality control method. The solubility of berberine hydrochloride in different auxiliary-materials were investigated, and the self-microemulsion formula was optimized by studying the self-microemulsifying efficiency. The content of berberine hydrochloride and cinnamaldehyde in the preparation were determined by HPLC. The optimal self-microemulsion formula was composed of OP, propanediol, cinnamon oil, and total alkaloid from Rhizoma Coptidis with the ratio of 4:8:3:6. The average size of the microemulsion particle was 15.8 nm; the average content of berberine hydrochloride and cinnamaldehyde in the preparation was above 20.0% and 10.0%, respectively. The acquired microemulsion with small particle size is stable. The determination method of berberine hydrochloride and cinnamaldehyde in the preparation is accurate and reliable.
18,973,026
[A new method to optimize the performance of JPEG2000-based PACS images' storage, transmission and display].
In connection with the efficiency problem of narrow-band PACS medical images transmission and display and following the DICOM 3.0 standard and JPEG2000 code stream properties of progressing transmission and free access, this paper presents a new parallel processing method of the images transmission and display. This method raises the performance of images' transmission, storage and display, and has been evaluated in the clinical medical diagnosis information system.
18,973,030
[Liquid gastric-emptying measurement using an electrical bio-impedance method].
This paper introduces a 4-electrode gastric-emptying measurement system using an electrical bio-impedance method by which gastric-emptying experiments of 24 healthy volunteers have been carried out. The test results show that the base impedance is stable, the average GET/2 is 8.78 +/- 1.76 min. The new system provides a new non-invasive measurement method for the clinical study on gastric-emptying functions.
18,973,033
[A method of controlling the X-ray generator with PLC technique].
This text probes into the usage of PLC controller which controls the X-ray generator's basic parameters.
18,973,039
[Development and applications of the extracorporeal control point module on multi-mode medical images].
This paper introduces a display module which can be used on multi-mode medical images. The module has a small size and can be easily used for point-selecting puncture diagnosis and treatment, and registration for image fusion control points.
18,973,042
Severe head injury: clinicians' awareness of the literature.
1. To determine the awareness of the literature concerning therapeutic manoeuvres in severe closed head injury (CHI) among Canadian critical care clinicians and neurosurgeons, 2. To identify factors that affect utilization of these manoeuvres, and 3. To compare reported appropriateness and frequency of use with #1 and #2. The study design was a systematic scenario-based survey of all neurosurgeons and critical care physicians treating patients with severe CHI in Canada. Fifty-nine of 99 neurosurgeons and 82 of 148 critical care physicians responded (57%). The majority of respondents were not able to identify the highest level of published evidence for most manoeuvres, except for the avoidance of corticosteroids (51%). The factor identified by most respondents as being most important in motivating use of any given manoeuvres was the level of published evidence (25%). Although reported appropriateness and frequency of use of most manoeuvres correlated well with each other, they did not correlate with awareness of evidence. In the case of corticosteroids, there was a strong correlation between non-use of steroids and awareness of evidence (R = -0.30, p = 0.0003). Respondents to this survey of Canadian physicians treating patients with severe head injury reported published evidence as being the most significant factor affecting use of a therapy. However, most respondents did not correctly identify the highest published level of evidence for most therapies. This study has identified difficulty with research translation that may have clinical implications.
18,973,063
Antioxidant enzyme activity and malondialdehyde concentration in the plasma and erythrocytes of patients with urticaria induced by nonsteroidal anti-inflammatory drugs.
It has been suggested that oxidative stress is a crucial event in some forms of urticaria. To evaluate the blood oxidant/antioxidant profile of patients suffering from urticaria induced by nonsteroidal anti-inflammatory drugs (NSAIDs). We measured the activity of the antioxidant enzymes copper-zinc superoxide dismutase (Cu/ZnSOD), glutathione peroxidase (GSH-Px), and catalase (CAT), and the levels of malondialdehyde (a marker of lipid peroxidation) in the plasma and erythrocytes of 12 females with NSAID-induced urticaria and in 19 healthy controls. The enzyme activity in plasma (CuZn/SOD) and in erythrocytes (CuZn/SOD, GSH-Px, and CAT) did not differ significantly between urticaria patients and controls. Moreover, the levels of malondialdehyde in plasma and erythrocytes did not differ significantly between the 2 groups. It seems that processes associated with urticaria induced by NSAIDs may not modify antioxidant enzyme activity and may not enhance lipid peroxidation in peripheral blood.
18,973,101