title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Transumbilical single-port laparoscopic partial nephrectomy. | To present the initial experience with laparoscopic partial nephrectomy (LPN) performed through a transumbilical single port. Between November 2007 and April 2008, five selected patients underwent single-port LPN (SPLPN) for renal tumours. All procedures were performed through a single intraumbilical multichannel laparoscopic port. A 2-mm grasper was inserted through a 2-mm Veres needle-port in the anterior axillary line to aid in tissue retraction and sutured renal reconstruction. The technique of standard multiport LPN was replicated, with the renal hilum clamped. SPLPN was successfully completed in four patients, while an additional 5-mm port was required in one patient. The median (range) tumour size was 3 (1-5.9) cm. The median (range) operating time was 270 (240-345) min and the estimated blood loss was 150 (100-600) mL. The median (range) warm ischaemia time was 20 (11-29) min. The median (range) length of the umbilical incision was 2.5 (2.5-4) cm. The median (range) hospital stay was 3(3-22) days. There were no intraoperative complications. All surgical margins were negative for tumour. There were no postoperative complications in four patients. One patient had postoperative bleeding and pulmonary embolism. SPLPN is technically feasible, albeit more challenging than conventional LPN. Proper case selection is essential. Advances in single-port specific instrumentation are needed before these procedures can become a part of mainstream urological laparoscopy. | 18,778,351 |
A RNA transcript (Heg) in mononuclear cells is negatively correlated with CD14 mRNA and TSH receptor autoantibodies. | During a study of gene expression of foxp3 in blood mononuclear cells we observed a DNA product of an unknown RNA fragment. The area of this peak correlated with CD14 mRNA in a small group of subjects. The sequence was localized to chromosome 1. We tested the hypothesis that gene expression of the poly A(-) transcript (designated Heg) in mononuclear cells was correlated with CD14 mRNA in normal subjects and with CD14 mRNA and TSH receptor autoantibodies in patients with acute and untreated Graves' disease. mRNA was expressed in amol/microg DNA. The main study groups were: (i) normal subjects; (ii) patients with early and untreated Graves' disease; and (iii) patients with Graves' disease studied after treatment. In 18 normal subjects and in 20 patients with treated Graves' disease CD14 mRNA was negatively correlated with Heg (P < 0.001). In 17 untreated patients with Graves' disease Heg and thyroid receptor autoantibodies were negatively correlated (P < 0.009). Incubation studies with mononuclear cells showed that the addition of a fragment of the central part of Heg (949 bases) to mononuclear cells decreased CD14 mRNA markedly to zero or nearly zero (P < 0.001). This response was not specific in the sense that siRNA and lipopolysaccharide also decreased CD14 mRNA, probably due to activation of the CD14/Toll-like receptor complex. Single-stranded RNA is likely to increase interferon production. Due to the anti-inflammatory effect Heg may also inhibit the early phase of TSH receptor autoantibody production. | 18,778,364 |
Impaired immune responses in streptozotocin-induced type I diabetes in mice. Involvement of high glucose. | Diabetes is widely believed to predispose to serious infections. However, the mechanisms linking diabetes and immunosuppression are not well defined. One potential mediator of the altered defence mechanisms is hyperglycaemia. It has been identified as the main factor contributing to the development of diseases associated with diabetes mellitus. In this study we analyse the immune response in diabetes and the direct effect of hyperglycaemia on T and B lymphocyte reactivity. Diabetes induced an early decrease in IgG levels in the secondary response. However, both primary responses against a T-cell-dependent or independent antigen were affected after 6 months of diabetes induction. T- and B- cell proliferation was only decreased at this time. To gain insight into the potential mechanisms involved, we evaluated the influence of hyperglycaemia over the immune response. Pre-incubation of lymph node and spleen cells in a high glucose (HG) containing medium led to a significant time- and dose-dependent decrease in T- and B-cell proliferation. This effect was associated with the presence of HG-derived supernatants. Still viable cells after HG exposition were able to improve their proliferative response when cultured with the mitogen in a fresh standard medium. HG diminished cell viability, increased apoptosis and induced oxidative stress in lymphocytes. These results indicate that HG concentrations can directly affect lymphoid cell growth. An increase in oxidative stress would be implicated in this deleterious effect. The possibility that prolonged exposure to pathologically HG concentrations would result in the immunosuppressive state observed in diabetes is also discussed. | 18,778,365 |
Deliberate practice and acquisition of expert performance: a general overview. | Traditionally, professional expertise has been judged by length of experience, reputation, and perceived mastery of knowledge and skill. Unfortunately, recent research demonstrates only a weak relationship between these indicators of expertise and actual, observed performance. In fact, observed performance does not necessarily correlate with greater professional experience. Expert performance can, however, be traced to active engagement in deliberate practice (DP), where training (often designed and arranged by their teachers and coaches) is focused on improving particular tasks. DP also involves the provision of immediate feedback, time for problem-solving and evaluation, and opportunities for repeated performance to refine behavior. In this article, we draw upon the principles of DP established in other domains, such as chess, music, typing, and sports to provide insight into developing expert performance in medicine. | 18,778,378 |
The waterpipe: time for action. | The waterpipe, known in many cultures under different shapes and names (e.g. hookah, shisha, narghile), is a centuries-old tobacco use method that is witnessing a world-wide surge in popularity. This popularity is most noticeable among youths, and is surpassing cigarette smoking among this group in some societies. Many factors may have contributed to the recent waterpipe spread, including the introduction of sweetened/flavored waterpipe tobacco (known as Maassel), its reduced-harm perception, the thriving café culture, mass media and the internet. The passage of smoke through water on its way to the smoker underlies much of the common misperception that waterpipe use is less harmful than cigarettes. The health/addictive profile of waterpipe compared to cigarettes is largely unresearched and is likely to be influenced by the properties of smoke, duration and frequency of use, type of tobacco used, volume of smoke inhaled and the contribution of charcoal. However, the accumulation of evidence about the harmful and addictive potential of waterpipe use is outpacing the public health response to this health risk. A timely public health and policy action is needed in order to curb the emerging waterpipe smoking epidemic. | 18,778,388 |
Hypothyroidism is associated with signs of endothelial dysfunction despite 1-year replacement therapy with levothyroxine. | Hypothyroidism is associated with elevated cardiovascular risk, not fully explained by classical risk factors. Instead, endothelial dysfunction may link hypothyroidism to atherosclerosis. The effect of levothyroxine substitution on endothelial function has been sparsely studied and the results are unclear. This study tested endothelial function as estimated by concomitant measurements of endothelial dependent vascular dilatory capacity and plasma concentration of von Willebrand factor antigen in patients with hypothyroidism and further examined the impact of subsequent levothyroxine substitution. Sixteen consecutive patients (13 women, 3 men, aged 46 +/- 11 years) with hypothyroidism were included and compared to 16 matched healthy controls (13 women, 3 men, aged 49 +/- 11 years). Patients with hypothyroidism were reexamined after 3, 6 and 12 months of levothyroxine substitution. Dilatory responses of the brachial artery to post-ischaemic increased blood flow (endothelium-dependent flow-associated dilatation) and to nitroglycerin (endothelium-independent nitroglycerin induced dilatation) were measured by ultrasound. Plasma concentrations of von Willebrand factor antigen were measured by ELISA. Flow-associated dilatation was impaired in patients with hypothyroidism as compared to controls (102.7 +/- 3.6 vs. 105.6 +/- 3.8%, P = 0.04) whereas no differences in plasma concentration of von Willebrand factor antigen were found. One year levothyroxine substitution did not improve flow-associated dilatation and was associated with an increase of the plasma von Willebrand factor antigen concentration. Hypothyroid patients are characterized by endothelial dysfunction sustained despite long-term levothyroxine substitution and potentially increasing the risk of atherosclerosis. Different estimates of endothelial dysfunction seem unequally influenced by hypothyroidism. | 18,778,398 |
Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice. | Storage of acetylcholine in synaptic vesicles plays a key role in maintaining cholinergic function. Here we used mice with a targeted mutation in the vesicular acetylcholine transporter (VAChT) gene that reduces transporter expression by 40% to investigate cognitive processing under conditions of VAChT deficiency. Motor skill learning in the rotarod revealed that VAChT mutant mice were slower to learn this task, but once they reached maximum performance they were indistinguishable from wild-type mice. Interestingly, motor skill performance maintenance after 10 days was unaffected in these mutant mice. We also tested whether reduced VAChT levels affected learning in an object recognition memory task. We found that VAChT mutant mice presented a deficit in memory encoding necessary for the temporal order version of the object recognition memory, but showed no alteration in spatial working memory, or spatial memory in general when tested in the Morris water maze test. The memory deficit in object recognition memory observed in VAChT mutant mice could be reversed by cholinesterase inhibitors, suggesting that learning deficits caused by reduced VAChT expression can be ameliorated by restoring ACh levels in the synapse. These data indicate an important role for cholinergic tone in motor learning and object recognition memory. | 18,778,400 |
Effect of a family psychoeducational program on relatives of schizophrenia patients. | Family psychoeducational programs have been shown to be effective in terms of knowledge acquirement and relapse prevention, but few studies have looked at whether one mode of educational method is more effective than another. The aim of the present study was to compare several modes of educational approaches and to elucidate which mode of education is more effective. A total of 110 relatives of 95 patients with schizophrenia received three types of family psychoeducational programs between January 1995 and September 2003: a small group with two sessions (P1), a large group with nine sessions (P2), and a large group with five sessions (P3). In addition to the demographic data, acquired knowledge was measured using the modified Knowledge About Schizophrenia Interview (KASI), family expressed emotion (EE), and relapse episodes. Overall there were significant increases in many KASI subcategory scores after the three programs, in mothers in particular. The change in KASI scores indicated that the low EE group was able to be highly educated and that the relatives of non-relapsers were more effectively educated. As for the mode of the family psychoeducational program, the P1 and P2 groups surpassed the P3 in terms of knowledge acquired. Effects of family psychoeducation may depend not on the number of members or sessions but on the time spent on the program per member. | 18,778,434 |
Relationship between exploratory eye movement, P300, and reaction time in schizophrenia. | Exploratory eye movement (EEM), P300 and reaction time (RT) tests may relate to the important parts of information processing in the human brain. Therefore the aim of the present study was to compare EEM, P300 and RT test data in schizophrenic and normal control groups to investigate whether schizophrenic patients have information processing abnormalities. In addition, the potential correspondence between the three tests was examined in order to investigate the information processing dysfunctions seen in schizophrenic patients. The EEM, P300 and RT performances were recorded in 34 schizophrenic and 36 normal control subjects. Ten parameters were measured: four from the EEM test (number of eye fixations, total eye scanning length, cognitive search score and responsive search score [RSS]); two from the P300 test (amplitude and latency); and four from the RT test (simple reaction time, index of reaction time crossover [IRT-crossover], set index and coefficient of variation). These parameters in the schizophrenic patients differed significantly from those in the control group. Additionally, there was a significant correlation between the RSS and the IRT-crossover in the schizophrenic patients. The present group comparisons (schizophrenia vs normal controls) are consistent with previous studies in that the abnormalities in EEM, P300 and RT tests in schizophrenic patients were able to be replicated. Moreover, based on the former psychological theory, it is reasonable to propose that the RSS is associated with the IRT-crossover. The present results may contribute to elucidation of the pathophysiological signature of schizophrenia. | 18,778,436 |
Predictors of subjective and objective quality of life in outpatients with schizophrenia. | In recent years, greater attention has been given to quality of life (QOL) in schizophrenia and several studies reported that negative and depressive symptoms and cognitive dysfunction are related to patient QOL. But because a variety of QOL measures have been used in the previous studies, there seems to be no unanimous predictors for subjective and objective QOL. The purpose of the present study was to elucidate the relationship between clinical variables and subjective and objective QOL in outpatients with schizophrenia, using schizophrenia disease-specific QOL measures. Particular attention was paid to cognitive function as a predictor of QOL. Schizophrenia symptoms of the Positive and Negative Syndrome Scale (PANSS) were divided into five factors: positive factor, negative factor, cognitive factor, emotional discomfort, and hostility. The study sample consisted of 84 schizophrenia outpatients. Subjective and objective QOL were assessed with Schizophrenia Quality of Life Scale (SQLS) and the Quality of Life Scale (QLS), respectively. Subjective QOL correlated significantly with emotional discomfort, positive factor, negative factor, extrapyramidal symptoms and cognitive factor, while objective QOL correlated with negative factor, cognitive factor, emotional discomfort, extrapyramidal symptoms, and dose of antipsychotics. Total score and three of four subscales in the QLS correlated significantly with cognitive factor, while cognitive factor had a significant correlation with only one of three scales of SQLS. Stepwise regression showed that subjective QOL was significantly predicted by emotional discomfort and extrapyramidal symptoms, while negative factor was the most important predictor of objective QOL. Cognitive dysfunction had a greater influence on objective QOL than subjective QOL. Treating depressive and negative symptoms and extrapyramidal symptoms might contribute to enhanced subjective and objective QOL. | 18,778,437 |
Relationship of attention-deficit-hyperactivity disorder symptoms, depressive/anxiety symptoms, and life quality in young men. | Attention-deficit-hyperactivity disorder (ADHD) continues to be among the most frequently missed of psychiatric diagnoses in adults because its presentation in adulthood so often mimics those of better-known disorders. The aim of the present study was to examine the relationship between ADHD symptoms, depression/anxiety symptoms, and life quality in young men. Nine hundred and twenty-nine draftees into the Taiwanese army completed the Adult ADHD Self-Report Scale (ASRS), the World Health Organization (WHO) Quality of Life-Brief Version, the Epworth Sleepiness Scale, the second edition of the Beck Depression Inventory, and the Beck Anxiety Scale. Based on high ASRS scores, a total of 328 adults (35.3%) were identified as having ADHD: 65 (7.0%) with definite ADHD and 263 (28.3%) with probable ADHD. The 328 subjects in the ADHD group had more severe depressive, anxiety symptoms and daytime sleepiness, and had poorer quality of life than the 601 controls (all P < 0.05). ADHD should be included in the differential diagnosis for young men presenting with anxiety, depression, daytime sleepiness, and poor quality of life. | 18,778,439 |
Restless legs symptoms with sleepiness in relation to mortality: 20-year follow-up study of a middle-aged Swedish population. | The aim of the present study was to investigate restless legs symptoms with concomitant daytime sleepiness as a risk factor for mortality in a middle-aged population. A cohort of 5102 subjects aged 30-65 years in mid-Sweden who responded to a postal questionnaire in 1983 was followed up. The questionnaire included questions about restless legs symptoms, daytime sleepiness, demographic and lifestyle variables, sleep habits, medical conditions and depression. Mortality data for the period 1983-2003 were collected and death certificates were available for all the 657 responders who died during the follow-up period. Restless legs symptoms with daytime sleepiness was reported by 10.3% and was associated with shorter night sleep time, several health problems and depression. During the follow-up period 379 men (21.6%) and 278 women (15.5%) died. A multivariate model adjusted for age, short night sleep time, lifestyle factors, medical conditions and depression showed that women reporting restless legs symptoms with daytime sleepiness had an excess mortality compared to women without restless legs symptoms and daytime sleepiness (hazard ratios, 1.85; 95% confidence interval, 1.20-2.85; P = 0.005). No influence on mortality risk was found in men reporting restless legs symptoms with daytime sleepiness. The occurrence of restless legs symptoms with daytime sleepiness in middle-aged women is associated with increased mortality risk. | 18,778,444 |
Dynamics of positional warfare malaria: Finland and Korea compared. | A sudden outbreak of vivax malaria among Finnish troops in SE-Finland and along the front line in Hanko peninsula in the southwest occurred in 1941 during World War II. The common explanation has been an invasion of infective Anopheles mosquitoes from the Russian troops crossing the front line between Finland and Soviet Union. A revised explanation is presented based on recent studies of Finnish malaria. The exact start of the epidemic and the phenology of malaria cases among the Finnish soldiers were reanalyzed. The results were compared with the declining malaria in Finland. A comparison with a corresponding situation starting in the 1990's in Korea was performed. The malaria cases occurred in July in 1941 when it was by far too early for infective mosquitoes to be present. The first Anopheles mosquitoes hatched at about the same time as the first malaria cases were observed among the Finnish soldiers. It takes about 3-6 weeks for the completion of the sporogony in Finland. The new explanation is that soldiers in war conditions were suddenly exposed to uninfected mosquitoes and those who still were carriers of hypnozoites developed relapses triggered by these mosquitoes. It is estimated that about 0.5% of the Finnish population still were carriers of hypnozoites in the 1940's. A corresponding outbreak of vivax malaria in Korea in the 1990's is similarly interpreted as relapses from activated hypnozoites among Korean soldiers. The significance of the mosquito induced relapses is emphasized by two benefits for the Plasmodium. There is a synchronous increase of gametocytes when new mosquitoes emerge. It also enables meiotic recombination between different strains of the Plasmodium. The malaria peak during the positional warfare in the 1940's was a short outbreak during the last phase of declining indigenous malaria in Finland. The activation of hypnozoites among a large number of soldiers and subsequent medication contributed to diminishing the reservoir of malaria and speeded up the eradication of the Finnish malaria. A corresponding evolution of Korean malaria is anticipated with relaxed tensions and decreasing troop concentrations along the border between South and North Korea. | 18,778,473 |
Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival. | We have engaged in an international program designated the Bank On A Cure, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma. We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, n = 70) versus long term progression-free survivors (greater than 3 years, n = 73) in two phase III clinical trials. Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival. While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes. A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma. The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS. | 18,778,477 |
Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer. | It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated. 46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI) classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material. A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier) was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy), whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively). The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they received. | 18,778,486 |
Association between obesity indices and blood pressure or hypertension: which index is the best? | The association between obesity and blood pressure is well documented and a series of obesity indices are used as risk factors or indicators of blood pressure and/or the presence of hypertension. The aim of the present study was to explore and determine which obesity index is the best indicator of blood pressure and the presence of hypertension among five frequently used simple anthropometric indices. Subjects (n 29 079) were selected by cluster sampling from fourteen Chinese general populations. Weight, height, waist circumference (WC), hip circumference and blood pressure were measured for each participant. BMI, waist:hip ratio (WHR), waist:stature ratio (WSR) and conicity index (CI) were calculated. Pearson correlation, multiple logistic regression, multivariate linear regression and receiver-operating characteristic (ROC) curve analyses were used. A total of 13 558 men and 15 521 women were investigated. All five obesity indices were positively correlated with blood pressures and hypertension. After adjusting for age, WSR in men and BMI in women had the greatest association with the presence of hypertension, irrespective of the statistical method used. BMI had the strongest correlation with continuous blood pressures in both genders. The present results indicate that hypertension is associated with different obesity indices in men and in women. The best indicator for hypertension is WSR in men while it is BMI in women. | 18,778,533 |
[Surgeon's role in diabetic retinopathy]. | Diabetic retinopathy (DR) is the most frequent cause of blindness during the patient's economically active years. The probability of developing this disease increases with the number of diabetic patients in our country, as well as their survival. In general, DR progression is predictable, from minimum changes (barely detectable through ophthalmoscopy) to advanced damage that requires surgical treatment. However, in Mexico, its late detection frequently necessitates retinal surgery. Current resources regarding vitreous and retinal surgery have improved anatomic results in the treatment of DR. Among the most important of these are panoramic vision systems, high-speed cutting equipment, small-caliber microsurgical instruments, endophotocoagulation, adjuvants such as heavy liquids, silicon oil and angiogenesis inhibitors, which have been the topic of several recent studies. | 18,778,535 |
A review of intensity-modulated radiation therapy. | Intensity-modulated radiation therapy (IMRT) is a sophisticated form of three-dimensional treatment planning and delivery. In some situations, IMRT allows more conformal radiation therapy to complex targets within the lung. As problems related to organ motion are increasingly addressed, the use of IMRT in the treatment of lung cancer, particularly in non-small cell lung cancer and mesothelioma, continues to rise. | 18,778,554 |
Insights from experimental studies into allodynia and its treatment. | Migraine is a common disorder that often is accompanied by cutaneous allodynia. Cutaneous allodynia on the head has been linked to sensitization of neurons in the trigeminal nucleus caudalis in animal models of migraine. In addition, migraine with allodynia is refractory to acute treatment with triptans. Understanding the mechanisms of allodynia, preventing its development, and finding effective treatments have become a priority in headache research. This paper reviews recent research on the pathogenesis of headache and the generation of allodynia. We discuss the regions of the nervous system that are involved in generating and maintaining headache pain and allodynia. We also discuss recent advances in the treatment of migraine based on translation research. | 18,778,578 |
The Why WAIT program: improving clinical outcomes through weight management in type 2 diabetes. | Targeting body weight, as an alternative model to targeting hemoglobin A(1c), is emerging as a viable and potentially cost-effective approach to diabetes management in clinical practice. Why WAIT (Weight Achievement and Intensive Treatment) is a 12-week multidisciplinary program for weight control and intensive diabetes management specifically designed for application in routine diabetes practice. The program, which is generally covered by insurance, is followed by continuous support aimed at long-term maintenance of weight loss and diabetes control. This model was effective in improving key metabolic abnormalities observed in diabetic patients. Eighty-two percent of participants achieved the target hemoglobin A(1c) of less than 7% on less diabetes medications. The achieved weight reduction after 12 weeks of intervention was maintained for an additional year. Future dissemination of this intervention model in routine clinical practice may require wider endorsement by third-party payers and support of governmental health care agencies to halt the progression of the epidemic of obesity and diabetes in the United States. | 18,778,592 |
Ultrasonographic examination of the deltoid ligament in bimalleolar equivalent fractures. | Lauge-Hansen supination-external rotation Stage IV ankle injuries may simulate a Stage II or Stage III injury radiographically if the medial disruption occurred through the deltoid ligament instead of the medial malleolus, making it difficult to determine whether an operation is indicated. Seventeen patients presented with radiographically isolated lateral malleolar fractures at the syndesmotic level. They were examined with ultrasonography for evaluation of the integrity of the deltoid ligament. Patients in whom ultrasonography showed complete rupture of the deltoid ligament received operative fixation of the ankle fracture, with exploration and repair of the deltoid ligament at the same time. Patients without complete rupture of the deltoid ligament were treated conservatively with a short leg cast for 6 weeks followed by an ankle brace for another 6 weeks. Nine male and six female patients completed the final clinical and radiographic evaluations. Ultrasonography showed complete rupture of the deltoid ligament in six patients. Exploration of the deltoid ligaments confirmed the sonographic findings in all these patients. In the remaining nine patients, the deltoid ligaments were not completely ruptured on ultrasound. These fractures were treated conservatively, and all healed uneventfully. All the 15 patients had good or fair results on the final evaluation. Ultrasonography is a convenient and accurate diagnostic tool to differentiate unstable bimalleolar-equivalent ankle fractures from an isolated lateral malleolar fracture. Thus, it can be helpful in the decision process for the treatment of choice for different fracture patterns. | 18,778,665 |
Effect of glycyrrhetinic acid on membrane band 3 in human erythrocytes. | Glycyrrhetinic acid (GA) is a hydrolytic product of the triterpene glycoside of glycyrrhizic acid, one of the main constituents of licorice root, which has long been studied, due to its several biological and endocrine properties. In this paper, GA was tested on human erythrocytes, and GA-induced alterations were compared with those caused by diamide, a mild oxidant inducing well-characterized cell/membrane alterations, and n-ethylmaleimide (NEM), as alkylating agent. In order to verify the biochemical steps underlying the action of GA, band 3 Tyr-phosphorylation level, enzyme recruitment and band 3 clustering in cells pre-incubated with GA before diamide treatment were all examined. Results show that GA, in a dose-dependent manner, prevents both diamide and NEM-induced band 3 Tyr-phosphorylation, but not GSH decrease caused by both compounds. In addition, diamide-induced band 3 clustering and IgG binding to altered cells were also completely reversed by GA pre-treatment. Also, when membrane sensitivity toward proteolytic digestion was tested, GA-treated cells showed high resistance to proteolysis. In conclusion, in human erythrocytes, GA is proposed to strengthen membrane integrity against both oxidative and proteolytic damage. | 18,778,682 |
Oleanolic acid derivative NPLC441 potently stimulates glucose transport in 3T3-L1 adipocytes via a multi-target mechanism. | The natural product oleanolic acid (OA) has been discovered to exhibit varied pharmacological functions including anti-inflammation, anti-tumor and anti-diabetes, while appropriate synthetic oleanolic acid derivatives seem to possess more potent activities. Here we identified a new oleanolic acid derivative, 3-beta-(2-carboxybenzoyloxy)-oleanolic acid (NPLC441), which functioned as a competitive PTP1B inhibitor and enhanced insulin-stimulated phosphorylation of IR and AKT in HepG2 cells. As an RXRalpha antagonist, it could selectively activate LXRalpha:RXRalpha heterodimer and increase the promoter activities of ABCA1 and ABCG1 genes in transient transfection assays. Quantitative RT-PCR and Western blot analyses suggested that NPLC441 could up-regulate GLUT4 expression in 3T3-L1 adipocytes, and such effect was further proved to be dependent on LXRalpha:RXRalpha activation. Moreover, 2-deoxyglucose uptake technology-based characterization demonstrated that this compound could stimulate glucose uptake in 3T3-L1 adipocytes. Finally, NPLC441 was observed to be able to suppress 11beta-HSD(1) expression in HepG2 cells, following the discovery that activation of LXRalpha:RXRalpha could repress the expression of 11beta-HSD(1). Compared with NPLC441, OA showed no effects on the transactivation of either LXRalpha:RXRalpha heterodimer or RXRalpha-LBD. Our work is thus expected to provide a new insight into the anti-diabetic application for oleanolic acid derivatives via multi-target mechanism, and NPLC441 could be used as a potential lead compound for further research. | 18,778,688 |
Membrane disruption: an early event of hair cell apoptosis induced by exposure to intense noise. | Membrane leakage has been found in hair cells undergoing apoptosis following exposure to intense noise. However, it is not known whether this membrane damage is the consequence of apoptotic degeneration or direct mechanical stress. The current study was designed to investigate whether membrane damage occurred before the onset of apoptosis and to determine the level of the membrane damage. Chinchillas were exposed to an impulse noise at 155 dB peak SPL. The noise-induced membrane damage was assessed functionally, using membrane tracers with graded molecular sizes (propidium iodide and FITC-dextrans with molecular sizes of 3, 40, 500, and 2000 kDa), and morphologically, using DiO staining and semithin sections. The study revealed two major findings. First, exposure to intense noise caused a rapid increase in membrane permeability, and the onset of membrane leakage preceded the manifestation of nuclear condensation. This indicates that the early membrane damage observed in apoptosis is the direct consequence of mechanical stress. Second, the level of membrane damage was severe, allowing the entry of 3 kDa and 40 kDa FITC-dextrans, but the membrane was not completely broken down, as evidenced by the preservation of the ability to exclude 500 kDa and 2000 kDa FITC-dextran molecules and the maintenance of the cell boundary. Notably, despite the membrane damage, hair cells continue to undergo the apoptotic process, leading to the generation of a type of apoptosis with early membrane damage. | 18,778,691 |
Transcriptional and epigenetic regulations of embryonic stem cells. | Embryonic stem cells (ESCs) are characterized by their broad developmental potential and the capacity to self-renew. The advent of high-throughput technologies has facilitated genome-wide studies of transcriptional network, resulting in an ever-increasing repertoire of transcription factors implicated in the maintenance of the embryonic stem cell state. While the transcriptional circuitry continues to expand, epigenetic regulation has also gained attention as an important process in stem cell function. Herein, we discuss the recent advancements made in understanding the transcriptional and epigenetic regulations of embryonic stem cells. | 18,778,721 |
Four different integrative recombination events involved in the mobilization of the gonococcal 5.2 kb beta-lactamase plasmid pSJ5.2 in Escherichia coli. | We identified and characterized four different recombination mechanisms involved in the cointegrative transfer of the Neisseria gonorrhoeae beta-lactamase plasmid pSJ5.2 by the gonococcal 41 kb tet(M) and the Gram negative self-transmissible plasmids N3 and R64 drd-33 using an Escherichia colirecA-background. Mobilization of pSJ5.2 by the tet(M) plasmid occurred by cointegration through a replicative transposition of two IS1 elements inserted upstream from the beta-lactamase gene of pSJ5.2 and creating a IS1::beta-lactamase hybrid promoter. Two types of recombinational events occurred within the 1.8 kb BamH1-HindIII fragment of pSJ5.2 with the N3 and R64 plasmids. A non-homologous recombination was found at coordinates 1817 and 2849 of pSJ5.2 with sequences from R64. A non-homologous recombination combined with an IS26-mediated one-ended transposition was found at coordinates 1817 and 3010 of pSJ5.2 with N3. In both recombinational events, a deletion of over 1 kb of pSJ5.2 occurred. The fourth recombination event was detected in the 1.0 kb BamH1-HindIII fragment of pSJ5.2 by homologous recombination between DNA from the truncated Tn3 resolvase gene of pSJ5.2 and the resolvase sequences from R64 and N3. | 18,778,732 |
Involvement of striatal lipid peroxidation and inhibition of calcium influx into brain slices in neurobehavioral alterations in a rat model of short-term oral exposure to manganese. | Manganese is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorder, characterized by excessive Mn accumulation, especially in astrocytes of basal ganglia and symptoms closely resembling idiopathic Parkinson's disease (PD). The purpose of this study was to evaluate behavioral and biochemical alterations in adult rats exposed for 30 days to 10 and 25mg/mL of MnCl(2) in their drinking water. MnCl(2) intoxicated rats showed impaired locomotor activity in comparison to control animals. Furthermore, lipid peroxidation were increased, delta-aminolevulinate dehydratase (delta-ALA-D, an enzyme sensitive to pro-oxidant situations) activity was inhibited and (45)Ca(2+) influx into striatal slices was decreased in rats exposed to 25mg/mL of Mn, indicating that this brain region was markedly affected by short-term Mn exposure. In contrast, Mn exposure was not associated with characteristic extrapyramidal effects and did not modify protein oxidation, suggesting that the striatal damage represents early stages of Mn-induced damage. In addition, treatment with Mn was associated with reduced body weight gain, but there were no discernible alterations in liver and kidney function. In conclusion, Mn caused increased oxidative stress and decreased (45)Ca(2+) influx into the striatum, which are likely linked to impaired locomotor activity, but not with the occurrence of orofacial dyskinesia. | 18,778,733 |
The effect of suppressing negative emotions on eating behavior in binge eating disorder. | Overeating may be a consequence of the suppression of negative emotions, by depleting self-control resources. This experiment investigated whether (a) there is a causal relationship between the suppression of negative emotions, negative mood, and overeating in people with binge eating disorder (BED) and whether (b) this relationship is increased in depressed people with BED. Sixty-six women with (full and sub-threshold) BED were shown an upsetting movie and then asked either to suppress their emotions or to react naturally. Subsequently, everyone participated in a taste task. After a decline, initial mood before watching the movie was restored after eating. Depressive symptomatology was positively correlated with caloric intake. Within the clinically depressed (Beck Depression Inventory-score>19) BED group, those who were most affected by the negative mood induction consumed the most calories. No differences were found between the two conditions with regard to caloric intake. No interaction effect was found between depressive symptoms and mood suppression. The hypothesis that suppression of negative emotion leads to overeating in (depressed) binge eaters was not born out. Overeating may serve as a means to (temporary) repair negative mood. | 18,778,742 |
Cannabinoid receptor 2 is increased in acutely and chronically inflamed bladder of rats. | Cannabinoid receptors 1 and 2 (CB1 and CB2) are G-protein coupled receptors that are expressed throughout the body. Cannabinoid receptors are expressed in the urinary bladder and may affect bladder function. The purpose of this study was twofold: to confirm the presence of cannabinoid receptors in the bladder, the L6/S1 spinal cord, and dorsal root ganglia (DRG), and to determine the effects of acute and chronic bladder inflammation on expression of cannabinoid receptors. Acute or chronic bladder inflammation was induced in rats by intravesical administration of acrolein. Abundance of CB1 and CB2 protein and their respective mRNA was determined using immunoblotting and quantitative real-time PCR, respectively. We confirmed the presence of CB1 and CB2 receptor protein and mRNA in bladder, L6-S spinal cord, and DRG. Acute bladder inflammation induced increased expression of CB2, but not CB1, protein in the bladder detrusor. Chronic bladder inflammation increased expression of bladder CB2 protein and mRNA but not CB1 protein or mRNA. Expression of CB1 or CB2 in spinal cord or DRG was unaffected by acute or chronic bladder inflammation. CB1 and CB2 receptors are present in the bladder and its associated innervation, and CB2 receptors are up-regulated in bladder after acute or chronic inflammation. CB2 receptors may be a viable target for pharmacological treatment of bladder inflammation and associated pain. | 18,778,751 |
The effect of intra-arterial papaverine on ECoG activity in the ketamine anesthetized rat. | The opium alkaloid papaverine (PPV) causes vasodilatation of the cerebral arteries through direct action on smooth muscle that reduces the constriction of smooth muscle. Intra-arterial papaverine (IAP) has been used widely to increase the regional cerebral blood flow in order to reverse the cerebral vasospasm that occurs during endovascular procedures. IAP-induced seizures have been reported, although PPV has anticonvulsive effects. This study determined the effects of IAP on electrocorticography (ECoG) in the ketamine anesthetized rats. We used 24 Sprague-Dawley male rats weighing 200-250 g. The animals were divided randomly into four groups: three treatment groups (groups 1-3) and a control (group 4). Groups 1, 2, and 3 were given 1, 7, and 14 mg/kg IAP, respectively. The ECoG was compared across groups. Our results indicated that IAP did not cause seizures and that it decreased the frequency of ketamine-induced epileptiform activity in the 14 mg/kg group. | 18,778,752 |
Investigation of the carbopol gel of solid lipid nanoparticles for the transdermal iontophoretic delivery of triamcinolone acetonide acetate. | The purpose of this study was to investigate solid lipid nanoparticles (SLN) hydrogel for transdermal iontophoretic drug delivery. Triamcinolone acetonide acetate (TAA), a glucocorticoids compound, was employed as the model drug. SLN containing the drug triamcinolone acetonide acetate (TAA-SLN) and their carbopol gel with stable physicochemical properties were prepared. The use of TAA-SLN carbopol gel as a vehicle for the transdermal iontophoretic delivery of TAA was evaluated in vitro using horizontal diffusion cells fitted with porcine ear skin. We found that the TAA-SLN gel possessed good stability, rheological properties, and high electric conductance. Transdermal penetration of TAA from TAA-SLN gel cross the skin tissue was significantly enhanced by iontophoresis. The enhancement of the cumulative penetration amount and the steady-state penetration flux of the penetrated drug were related to the particle size of TAA-SLN and the characteristics of the applied pulse electric current, such as density, frequency, and on/off interval ratio. These results indicated that SLN carbopol gel could be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions. | 18,778,760 |
Central effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice. | Petiveria alliacea L. (tipi) a shrub from Phytolaccaceae family is popularly used in folk medicine for treating a wide variety of disorders in South and Central America. To investigate the neuropharmacological properties on experimental animals. The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in the classical behavioral models (open-field, elevated plus maze-EPM, rotarod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests) using mice. These fractions were administered intraperitoneally and orally to female mice at single doses of 100 and 200mg/kg. All these fractions decreased the locomotor activity, rearing and grooming in the open-field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rotarod test. On EPM, all the fractions of tipi presented a significant reduction on the time of permanence in the open arms, indicating an absence of anxiolytic-like effect. In addition, the fractions increased the immobility time in the forced swimming test and potentiated pentobarbital-induced sleeping time in mice, confirmed a probable sedative and central depressant effect. Furthermore, the fractions increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant. Our results suggest that the fractions of P. alliacea L. contains biologically active substance(s) that might be acting in the CNS and have significant depressant and anticonvulsant potentials, supporting folk medicine use of this plant. | 18,778,763 |
Application of high pressure laser flash photolysis in studies on selected hemoprotein reactions. | This article focuses on the application of high pressure laser flash photolysis for studies on selected hemoprotein reactions with the objective to establish details of the underlying reaction mechanisms. In this context, particular attention is given to the reactions of small molecules such as dioxygen, carbon monoxide, and nitric oxide with selected hemoproteins (hemoglobin, myoglobin, neuroglobin and cytochrome P450(cam)), as well as to photo-induced electron transfer reactions occurring in hemoproteins (particularly in various types of cytochromes). Mechanistic conclusions based on the interpretation of the obtained activation volumes are discussed in this account. | 18,778,796 |
Risk factors of liver dysfunction after extended hepatic resection in biliary tract malignancies. | Postoperative hepatic insufficiency is a critical complication after extended hepatic resection in patients with biliary tract malignancies, the majority of whom suffer from obstructive jaundice. The aim of this study was to assess clinical parameters linked to this type of liver dysfunction. A total of 111 patients were retrospectively reviewed. Patient background, pre- and intraoperative parameters, and a ratio of remnant liver volume/entire liver volume (RLV/ELV) as a volumetric parameter were compared between patients with and without postoperative hyperbilirubinemia and subsequent fatal outcome. Logistic regression indicated that only RLV/ELV ratio was an independent factor influencing postoperative hyperbilirubinemia, and RLV/ELV ratio and indocyanine green retention rate at 15 minutes (ICG-R15) were factors affecting survival. Patients with RLV/ELV less than 40% had 7.6 times the risk of postoperative hyperbilirubinemia, while no patients with RLV/ELV greater than 40% and ICG-R15 less than 25% died of liver failure. The RLV/ELV ratio was the factor with the greatest impact on liver dysfunction after extended hepatectomy in patients with biliary tract malignancies. | 18,778,802 |
Efficacy of diagnostic upper-node procedures during laryngectomy for glottic carcinoma. | Regional recurrence of glottic squamous cell carcinoma was evaluated in patients with a clinically N0 neck who underwent selective upper-node dissection (SUND) or selective upper-node inspection (SUNI; surgical visualization and palpation of jugular lymph nodes at levels II and III) during (salvage) laryngectomy. In 152 patients, 291 clinically N0 (139 bilateral and 13 contralateral) necks were evaluated for occult neck metastases by SUNI or SUND during (salvage) laryngectomy. Occult neck metastases were identified with SUNI or SUND in 7% of the necks (21 of 291). In 4% (n = 11) of the remaining 270 necks, regional recurrence was detected during follow-up evaluation. Thus, in these 8 patients, SUNI or SUND seemed to have failed. SUND or SUNI of levels II and III during (salvage) laryngectomy identified the vast majority of patients who needed extensive neck treatment. In the N0 necks, these techniques led to less morbidity than elective neck dissection. | 18,778,803 |
Life-threatening postoperative pancreatic fistula (grade C) after pancreaticoduodenectomy: incidence, prognosis, and risk factors. | Pancreatic fistula (PF) is one of the most common postoperative complications of pancreatoduodenectomy (PD). A recent International Study Group on Pancreatic Fistula (ISGPF) definition grades the severity of PF according to the clinical impact on the patient's hospital course. Although PF is generally treated conservatively (grade A), some cases may require interventional procedures (grade B) or may be life-threatening and necessitate emergency reoperation (grade C). The aim of the present study was to evaluate the incidence of postoperative grade C PF after PD and to assess the prognosis and risk factors for this life-threatening condition. Between January 2000 and December 2006, 680 consecutive patients underwent PD in 5 digestive surgery departments in the northwest region of France (Lille, Amiens, Rouen, and Caen). PF was defined as drain output of any measurable volume of fluid on or after postoperative day 3 with amylase content greater than 3 times the serum amylase activity (ISGPF guidelines). To identify possible risk factors for grade C PF, we reviewed the records of 111 (16.3%) patients with postoperative PF and compared grade C cases with grade A+B cases. The median age was 59 years (range 22-87). The male-to-female ratio was 1.6:1. Fifty-six (50.4%) PDs were performed via pancreaticogastrostomy and 55 via pancreaticojejunostomy. Overall mortality was 2% (n = 14). Grade C PF was observed in 36 (32%) patients, of whom 17 (47%) had sepsis due to an abdominal collection, 16 (44%) had postoperative bleeding, 10 (27.7%) had bleeding associated with abdominal collection, and 3 (9%) had multi-organ failure due to other causes. Of these 36 patients, 35 (97%) underwent reoperation. The mortality rate in grade C PF patients was 38.8%. The major causes of death were sepsis (n = 6) and recurrent bleeding after reoperation (n = 5). Grade C PF increased the duration of postoperative hospitalization (46 vs 29 days, P < .001). Univariate analysis showed that peroperative soft pancreatic parenchyma, peroperative blood transfusion, and postoperative bleeding were significant risk factors for grade C PF, with P values of .011, .003, and .001, respectively. No risk factors for grade C PF were identified in a multivariate analysis. The sensibility, specificity, positive predictive value, and negative predictive value of the presence of the 3 risk factors for grade C PF were 13.89%, 100%, 100%, and 70.75%, respectively. Sixteen percent of patients had PF after PD. Among them, 30% had grade C PF, with a mortality rate of about 40%. Achievement of a 100% predictive positive value for grade C PF after PD in individuals with 3 discriminant risk factors (peroperative soft pancreatic parenchyma, peroperative transfusion, and postoperative bleeding) is a first step towards the identification of high-risk patients who should be managed differently from other patients with PF during or after PD. | 18,778,804 |
Does the duration of surgery affect outcomes in patients undergoing coronary artery bypass grafting? | Numerous predictors of coronary artery bypass grafting (CABG) outcomes have been identified. We aimed to determine whether the duration of surgery independently predicts outcome in patients undergoing CABG. We retrospectively reviewed data from 337 patients (mean age 62 +/- 7 years) who underwent CABG consecutively at our institution between January 2005 and December 2006. Duration of surgery correlated positively with length of both surgical intensive care unit (SICU) stay (r = .147, P = .004) and ventilator support (r = .097, P = .038) in univariate analysis, but only with length of SICU stay (P = .01) in a multivariate logistic regression after confounding factors were controlled for in the model. The regression coefficient was .006; every additional 30 minutes of surgery time was associated with 4.32 more hours of SICU stay. Duration of surgery was not associated with survival (P > .05). Although duration of surgery did not affect short-term survival after CABG, surgical duration independently predicted length of SICU stays. Efforts to reduce the length of operations may promote more efficient use of hospital resources. | 18,778,805 |
Effect of tamoxifen treatment on global and insulin-like growth factor 2-H19 locus-specific DNA methylation in rat spermatozoa and its association with embryo loss. | To determine the effect of tamoxifen treatment on global and insulin-like growth factor 2-H19 imprinting control region (Igf2-H19 ICR)-specific DNA methylation in rat spermatozoa and analyze its association with postimplantation loss. Experimental prospective study. Animal research and academic research facility. Male and female 75-day-old Holtzman rats. Global and Igf2-H19 ICR-specific DNA methylation was analyzed in an epididymal sperm sample in control and tamoxifen-treated rats at a dose of 0.4 mg tamoxifen/kg/day. DNA methylation status was correlated to postimplantation loss in females mated with tamoxifen-treated males. Global sperm DNA methylation level, methylation status of Igf2-H19 ICR in sperm, postimplantation loss. Tamoxifen treatment significantly reduced methylation at Igf2-H19 ICR in epididymal sperm. However, the global methylation level was not altered. A mating experiment confirmed a significant increase in postimplantation loss upon tamoxifen treatment and showed significant correlation with methylation at Igf2-H19 ICR. Reduced DNA methylation at Igf2-H19 ICR in rat spermatozoa upon tamoxifen treatment indicated a role of estrogen-associated signaling in the acquisition of paternal-specific imprints during spermatogenesis. In addition, association between DNA methylation and postimplantation loss suggests that errors in paternal imprints at Igf2-H19 ICR could affect embryo development. | 18,778,817 |
Serum levels of soluble vascular cell adhesion molecule-1, tumor necrosis factor-alpha, and interleukin-6 in in vitro fertilization cycles. | To assess whether gonadotropin-induced changes in E(2) alter serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and proinflammatory cytokines. Prospective collection of serum in patients undergoing IVF. University hospital. Twenty-four infertile women. Serum collection at baseline, in the mid and late follicular phases, at oocyte retrieval, and in the mid and late luteal phases. Samples were assayed for sVCAM-1, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and E(2). The VCAM-1 was maximally suppressed in the luteal phase. Luteal sVCAM-1 levels correlated [1] positively with the patient's age, units of gonadotropins, day 3 FSH levels and [2] negatively with [a] the follicular, retrieval, and luteal E(2) levels and [b] the number of preovulatory follicles and oocytes retrieved. Similar correlations were noted in the late luteal phase. Serum TNF-alpha reached a peak in the mid-follicular phase and a nadir in the luteal phase. The TNF-alpha levels at retrieval correlated [1] positively with the patient's age and [2] negatively with E(2) and number of preovulatory follicles and retrieved oocytes. The IL-6 levels were suppressed in the follicular phase and correlated negatively with E(2) levels. Changes in E(2) levels seen during gonadotropin stimulation significantly alter VCAM-1 expression and induce changes in serum IL-6 and TNF-alpha levels. | 18,778,820 |
Simultaneous characterization of selenium and arsenic analytes via ion-pairing reversed phase chromatography with inductively coupled plasma and electrospray ionization ion trap mass spectrometry for detection applications to river water, plant extract and urine matrices. | With an increased awareness and concern for varying toxicities of the different chemical forms of environmental contaminants such as selenium and arsenic, effective methodologies for speciation are paramount. In general, chromatographic methodologies have been developed using a particular detection system and a unique matrix for single element speciation. In this study, a routine method to speciate selenium and arsenic in a variety of "real world" matrices with elemental and molecular mass spectrometric detection has been successfully accomplished. Specifically, four selenium species, selenite, selenate, selenomethionine and selenocystine, and four arsenic species, arsenite, arsenate, monomethlyarsonate and dimethylarsinate, were simultaneously separated using ion-pairing reversed phase chromatography coupled with inductively coupled plasma and electrospray ionization ion trap mass spectrometry. Using tetrabutylammonium hydroxide as the ion-pairing reagent on a C(18) column, the separation and re-equilibration time was attained within 18min. To illustrate the wide range of possible applications, the method was then successfully applied for the detection of selenium and arsenic species found naturally and spiked in river water, plant extract and urine matrices. | 18,778,826 |
Optimisation of asymmetrical flow field flow fractionation for environmental nanoparticles separation. | The fractionation of natural nanoparticles by Asymmetrical Flow Field Flow Fractionation (As-Fl-FFF) was optimised by considering the following operating conditions: ionic strength, surfactant concentration and crossflow rate. The method performances such as fractionation recovery and fractionation efficiency were evaluated on a stable solution of colloidal-size natural inorganic particles. The online multi-detection by ultraviolet/visible spectrophotometer (UV) and multi-angle laser light scattering (MALLS) provided the monitoring of the sample during the separation and the evaluation of the fractionation efficiency. The lowest ionic strength and surfactant concentrations (i.e. 10(-3) mol L(-1) NH4NO3 and 3 x 10(-4) mol L(-1) SDS) allowed to obtain the highest sample recovery and lowest loss of the largest particles. The crossflow rate was investigated in order to avoid significant membrane-sample interaction. The applicability of the fractionation in optimised conditions was evaluated on a natural soil leachate, which was filtrated with different filter cut-offs. Filtration efficiency was stressed by the decrease of the large unfractionated particle influence in the void volume. For the first time, robust operating conditions were proposed to well size-fractionate and characterize soil nanoparticles within a single multi-detection analysis. | 18,778,831 |
Strategies for monitoring the emerging polar organic contaminants in water with emphasis on integrative passive sampling. | Although polar organic contaminants (POCs) such as pharmaceuticals are considered as some of today's most emerging contaminants few of them are regulated or included in on-going monitoring programs. However, the growing concern among the public and researchers together with the new legislature within the European Union, the registration, evaluation and authorisation of chemicals (REACH) system will increase the future need of simple, low cost strategies for monitoring and risk assessment of POCs in aquatic environments. In this article, we overview the advantages and shortcomings of traditional and novel sampling techniques available for monitoring the emerging POCs in water. The benefits and drawbacks of using active and biological sampling were discussed and the principles of organic passive samplers (PS) presented. A detailed overview of type of polar organic PS available, and their classes of target compounds and field of applications were given, and the considerations involved in using them such as environmental effects and quality control were discussed. The usefulness of biological sampling of POCs in water was found to be limited. Polar organic PS was considered to be the only available, but nevertheless, an efficient alternative to active water sampling due to its simplicity, low cost, no need of power supply or maintenance, and the ability of collecting time-integrative samples with one sample collection. However, the polar organic PS need to be further developed before they can be used as standard in water quality monitoring programs. | 18,778,833 |
Sleep problems and suicidality in the National Comorbidity Survey Replication. | Links between sleep problems and suicidality have been frequently described in clinical samples; however, this issue has not been well-studied in the general population. Using data from a nationally representative survey, we examined the association between self-reported sleep difficulties and suicidality in the United States. The WHO Composite International Diagnostic Interview was used to assess sleep problems and suicidality in the National Comorbidity Survey Replication (NCS-R). Relationships between three measures of sleep (difficulty initiating sleep, maintaining sleep, early morning awaking), and suicidal thoughts, plans, and attempts were assessed in logistic regression analyses, while controlling for demographic characteristics, 12-month diagnoses of mood, anxiety and substance use disorders, and chronic health conditions. In multivariate models, the presence of any of these sleep problems was significantly related to each measure of suicidality, including suicidal ideation (OR=2.1), planning (OR=2.6), and suicide attempt (OR=2.5). Early morning awakening was associated with suicidal ideation (OR=2.0), suicide planning (OR=2.1), and suicide attempt (OR=2.7). Difficulty initiating sleep was a significant predictor of suicidal ideation and planning (ORs: 1.9 for ideation; 2.2 for planning), while difficulty maintaining sleep during the night was a significant predictor of suicidal ideation and suicide attempts (ORs: 2.0 for ideation; 3.0 for attempt). Among community residents, chronic sleep problems are consistently associated with greater risk for suicidality. Efforts to develop comprehensive models of suicidality should consider sleep problems as potentially independent indicators of risk. | 18,778,837 |
Optimization of nutrient component for diesel oil degradation by Rhodococcus erythropolis. | A novel bacterium T7-2 was isolated from the oil-polluted sea-bed mud of Bohai Sea, northern China, which can degrade diesel oil at 15 degrees C. This bacterium was identified as a strain of Rhodococcus erythropolis according to its 16S rDNA gene. In order to enhance degradation efficiency, a five-level, three-factor central composite design was employed to optimize the nutrition supplied to artificial seawater. The results indicate that a supplement of 2.53 g (NH(4))(2)SO(4)L(-1), 2.75 g Na(2)HPO(4)L(-1) and 0.01 g yeast extract L(-1) to artificial seawater increases the degradation rate from 12.61% to 75% within 7d. | 18,778,839 |
The genetic diversity of human noroviruses detected in river water in Korea. | We studied the genetic diversity of human noroviruses in river waters by RT-nested PCR and phylogenetic analysis. During 2002-2003, water samples were collected from four rivers in Gyeonggi Province, South Korea. Among the 58 samples, 32 (55.2%) and 26 (44.8%) showed positive results with noroviruses belonging to genogroups I (GI) and II (GII), respectively. The phylogenetic analysis grouped 8 and 7 genotypes in GI and GII, respectively. The major types were GI/1, GI/13, and GII/15, and GI/1 and GI/3 were temporarily distributed. Most GI- and GII-grouped strains were closely related to the reference strains from neighboring countries, China and Japan, and GII/4-related strains had similar sequences to strains recognized as worldwide epidemic outbreaks. The strains circulating between countries are of particular concern to the outbreaks of noroviral diseases in Korea and must be periodically monitored in the natural environments. | 18,778,846 |
Relationships among specific reasons for culling, reproductive data, and gross morphology of the genital tracts in gilts culled due to reproductive failure in Thailand. | The present study aims to investigate genital organs of replacement gilts culled due to reproductive failure, and the relationship between gross morphological findings and historical reproductive data. The study was conducted from July 2005 to September 2006 and included a random sample of 200 genital organs from six swine herds in Thailand. Historical data and the reasons for culling were analyzed. Gross morphological examinations focused on the normality and abnormalities of the ovaries, as well as the remainder of the reproductive tract. Descriptive statistics and frequency analysis were conducted for all reproductive parameters. On average, the gilts were culled at 321.2+/-51.1d of age, at a body weight of 145.3+/-24.2kg. Gilts expressed first estrus at 253.2+/-32.7d and were artificially inseminated for the first time at 268.2+/-30.8d of age. The interval from entry to culling averaged 96.9+/-53.7d. Reasons for culling included anestrus (44.0%), vaginal discharge (20.5%), repeat breeding (15.5%), not being pregnant (10.0%), and miscellaneous causes (10.0%). Overall, 50.5% of gilts had normal genital organs, whereas 49.5% had at least one abnormality. Abnormalities of the ovary, oviduct, uterus, cervix and vagina-vestibule were found in 15.5%, 14.0%, 22.0%, 16.2%, and 17.6% of the gilts, respectively. The most common post-mortem abnormalities included endometritis (14.0%), cystic ovaries (10.5%) and congenital abnormalities of the reproductive tract (8.0%). Of the gilts culled due to anestrus, 52.2% were pre-pubertal. Most of the gilts culled due to vaginal discharge or repeat breeding had been cycling (90.2% and 96.8%, respectively). | 18,778,851 |
Physicians' multitasking and incentives: empirical evidence from a natural experiment. | We analyse how physicians respond to contractual changes and incentives within a multitasking environment. In 1999 the Quebec government (Canada) introduced an optional mixed compensation (MC) system, combining a fixed per diem with a partial (relative to the traditional fee-for-service (FFS) system) fee for services provided. We combine panel survey and administrative data on Quebec physicians to evaluate the impact of this change in incentives on their practice choices. We highlight the differentiated impact of incentives on various dimensions of physician behaviour by considering a wide range of labour supply variables: time spent on seeing patients, time devoted to teaching, administrative tasks or research, as well as the volume of clinical services and average time per clinical service. Our results show that, on average, the reform induced physicians who changed from FFS to MC to reduce their volume of (billable) services by 6.15% and to reduce their hours of work spent on seeing patients by 2.57%. Their average time spent per service increased by 3.81%, suggesting a potential quality-quantity substitution. Also the reform induced these physicians to increase their time spent on teaching and administrative duties (tasks not remunerated under the fee-for-service system) by 7.9%. | 18,778,862 |
Changes in leaf water relations, gas exchange, growth and flowering quality in potted geranium plants irrigated with different water regimes. | Geranium plants are an important part of urban green areas but suffer from drought, especially when grown in containers with a limited volume of medium. In this experiment, we examined the response of potted geraniums to different irrigation levels. Geranium (Pelargoniumxhortorum L.) seedlings were grown in a growth chamber and exposed to three irrigation treatments, whereby the plants were irrigated to container capacity (control), 60% of the control (moderate deficit irrigation, MDI), or 40% of the control (severe deficit irrigation, SDI). Deficit irrigation was maintained for 2 months, and then all the plants were exposed to a recovery period of 112 month. Exposure to drought induced a decrease in shoot dry weight and leaf area and an increase in the root/shoot ratio. Height and plant width were significantly inhibited by the SDI, while flower color parameters were not affected by deficit treatment. The number of wilting and yellow leaves increased, coinciding with the increase in the number of inflorescences and open flowers. Deficit irrigation led to a leaf water potential of about -0.8MPa at midday, which could have caused an important decrease in stomatal conductance, affecting the photosynthetic rate (Pn). Chlorophyll fluorescence (Fvm) values of 0.80 in all treatments throughout the experiment demonstrate the lack of drought-induced damage to PSII photochemistry. Pressure-volume analysis revealed low osmotic adjustment values of 0.2MPa in the SDI treatment, accompanied by increases in the bulk tissue elastic modulus (epsilon, wall rigidity) and resulting in turgor loss at lower leaf water potential values (-1.38MPa compared with -1.0MPa for the control). Leaf water potential values throughout the experiment below those for Psitlp were not found at any sampling time. By the end of the recovery period, the leaf water potential, stomatal conductance and net photosynthesis had recovered. We infer from these results that moderate deficit irrigation in geranium reduced the consumption of water, while maintaining the good overall quality of plants. However, when SDI was applied, a reduction in the number of flowers per plant was observed. | 18,778,872 |
Changes in the protein profile of Quercus ilex leaves in response to drought stress and recovery. | To characterize the molecular response of holm oak to drought stress and its capacity to recover 9-month-old Quercus ilex seedlings were subjected to three treatments for a 14-d period: (i) continuous watering to field capacity (control plants, W), (ii) no irrigation (drought treatment, D), and (iii) no irrigation for 7d followed by a watering period of 7d (recovery treatment, R). In drought plants, leaf water potential decreased from -0.72 (day 0) to -0.99MPa (day 7), and -1.50MPa (day 14). Shoot relative water content decreased from 49.3% (day 0) to 47.7% (day 7) and 40.8% (day 14). Photosystem II quantum yield decreased from 0.80 (day 0) to 0.72 (day 7) and 0.73 (day 14). Plants subjected to water withholding for 7d reached, after a 7-d rewatering period, values similar to those of continuously irrigated control plants. Changes in the leaf protein pattern in response to drought and recovery treatments were analyzed by using a proteomic approach. Twenty-three different spots were observed when comparing the two-dimensional electrophoresis profile of control to both drought and recovered plants. From these, 14 proteins were identified from tryptic peptides tandem mass spectra by using the new Paragon algorithm present in the ProteinPilot software. The proteins identified belong to the photosynthesis, carbohydrate and nitrogen metabolism, and stress-related protein functional categories. | 18,778,874 |
Immucillins in custom catalytic-site cavities. | Neighboring-group participation in the reaction catalyzed by purine nucleoside phosphorylase involves a compression mode between the 5'- and 4'-ribosyl oxygens, facilitated by His257. The His257Gly mutant opens a space in the catalytic site. Hydrophobic 5'-substituted Immucillins are transition-state analogue inhibitors of this mutant enzyme. Dissociation constants as low as 2pM are achieved, with K(m)/K(d) as high as 400,000,000. | 18,778,937 |
Tuberous sclerosis: localizing the epileptogenic tuber with synthetic aperture magnetometry with excess kurtosis analysis. | The hallmark of tuberous sclerosis is the presence of multiple cortical tubers. Identifying the epileptogenic tubers is difficult and often requires invasive intracranial electroencephalograph (EEG) monitoring. We report on a patient with tuberous sclerosis upon whom the novel magnetoencephalography (MEG) technique of synthetic aperture magnetometry (SAM) with excess kurtosis (g2) analysis was performed for localization of the epileptogenic tuber. Simultaneous electroencephalography (EEG) was also performed. MEG data, as analyzed by SAM(g2), were superimposed on the patient's MRIs. In the fluid attenuated inversion recovery MRIs, several tubers and subependymal nodules could be identified, with the largest tubers being located in the right frontal and left anteriotemporal regions. Despite multiple cortical lesions existing, the SAM(g2) images showed a single large tuber and surrounding epileptogenic tissue in the left temporal cortex. We suggest that MEG with SAM(g2) analysis may be clinically useful for the accurate identification of epileptogenic tubers in patients with tuberous sclerosis. | 18,778,940 |
Endoscopic management of pancreatic pseudocyst in children-a long-term follow-up. | Literature on long-term outcome after endoscopic management of pediatric pancreatic pseudocyst is not available. The aim of the present study is to report long-term outcome after endoscopic drainage of pancreatic pseudocyst in children. Nine patients younger than 15 years, subjected to endoscopic pseudocyst drainage, were included in this study (between 1994 and 2004). Eight patients were subjected to endoscopic cystogastrostomy and stenting, whereas 1 patient was subjected to cystoduodenostomy and stenting. A follow-up of patients was done at 1 month and at 2 to 10 years after drainage. Endoscopic retrograde cholangiopancreatography (ERCP) was done in 2 patients at the time of drainage, and it was repeated in both the patients at the time of final follow-up. Mean age of the patients was 9.6 years. Trauma was the most common cause (n = 8). Mean follow-up of these patients was 5.7 years (2-10 years). No recurrence was seen in any patient. Endoscopic retrograde cholangiopancreatography revealed complete pancreatic duct block in prevertebral region in 2 posttraumatic patients, and it was persisting on repeat ERCP at final follow-up. Endoscopic drainage of pancreatic pseudocyst is safe in children with a very good long-term outcome. Pancreatic duct block seen on ERCP may not be clinically important on long-term follow-up. | 18,778,998 |
Cervical spine injury in young children: a National Trauma Data Bank review. | Blunt cervical spine injury (CSI) is rare in the pediatric population. The objective of this study was to better characterize the incidence and type of CSI in young children (age <3 years) using a large, trauma center-based data set. The National Trauma Data Bank (NTDB) was reviewed for the period January 2001 to December 2005 for patients younger than 3 years of age with a blunt CSI (International Classification of Diseases, Ninth Revision, 805x, 806x, 952x). Demographic, injury, and outcome information were reviewed. Data management was performed using SAS (SAS, Cary, NC) and Stata (Stata Corp, College Station, TX). Patients with CSI were compared to patients without CSI of similar age. Means were compared with the Wilcoxon rank sum test, medians were compared with a nonparametric test, and count data were compared with the chi(2) test, with significance set at <.05. For the period of review, 95,654 young children (age <3 years) with blunt trauma were identified in the NTDB. The overall population had a median Injury Severity Score (ISS) of 4, and most patients (77.01%) had a Glasgow Coma Score (GCS) of 15. There were 1523 (1.59%) patients with a CSI (spinal cord and/or column), including 366 patients (0.38%) with a spinal cord injury (with or without column injury) and 182 (0.19%) with an isolated spinal cord injury (SCIWORA). The CSI and non-CSI populations did not differ regarding median GCS (15 for both groups), but the CSI population had a significantly higher median ISS (14 vs 4, respectively; P < .001). Compared to patients without CSI, the CSI population was more likely to die in the emergency department (2.04% vs 1.25%; P = .007) or be admitted to the intensive care unit (45.3% vs 16.9%; P < .001). Nearly half of all cervical spine fractures (48%) and more than half of cervical spinal cord injuries (53%) were in the lower cervical spine (C5-7). MVCs were the most common injury mechanism (66%) followed by falls (15%). A CSI was observed in 3.2% of all motor vehicle crashes (MVCs). In this trauma center population, these findings confirm the infrequency of blunt CSI in the youngest (age <3 years) trauma patients. The frequency of injuries to the lower cervical spine is higher than previously appreciated. MVCs are the most likely injury mechanism for this potentially devastating injury. | 18,779,013 |
Active for life: final results from the translation of two physical activity programs. | Most evidence-based programs are never translated into community settings and thus never make a public health impact. Active for Life (AFL) was a 4-year translational initiative using a pre-post, quasi-experimental design. Data were collected from 2003 to 2007. Analyses were conducted in 2005 and 2008. Nine lead organizations at 12 sites participated. Active Choices participants (n=2503) averaged 65.8 years (80% women, 41% non-Hispanic white). Active Living Every Day (ALED) participants (n=3388) averaged 70.6 years (83% women, 64% non-Hispanic white). In AFL, Active Choices was a 6-month telephone-based and ALED a 20-week group-based lifestyle behavior change program designed to increase physical activity, and both were grounded in social cognitive theory and the transtheoretical model. The interventions were evaluated in Years 1, 3, and 4. An adapted shortened ALED program was evaluated in Year 4. Moderate- to vigorous-intensity physical activity, assessed with the CHAMPS self-reported measure. Posttest survey response rates were 61% for Active Choices and 70% for ALED. Significant increases in moderate- to vigorous-intensity physical activity, total physical activity, and satisfaction with body appearance and function, and decreases in BMI were seen for both programs. Depressive symptoms and perceived stress, both low at pretest, also decreased over time in ALED. Results were generally consistent across years and sites. Active Choices and ALED were successfully translated across a range of real-world settings. Study samples were substantially larger, more ethnically and economically diverse, and more representative of older adult's health conditions than in efficacy studies, yet the magnitude of effect sizes were comparable. | 18,779,028 |
A novel technique for distal locking of intramedullary nail based on two non-constrained fluoroscopic images and navigation. | Distal locking is one of the most difficult steps in intramedullary nailing. Numerous methods can help the surgeon, but all are time-consuming and involve much irradiation. We have developed and tested a new method based on only two fluoroscopic shots that do not need to be taken in the axes of the holes. This avoids requiring the presence of an experienced fluoroscopy operator to accurately adjust the imaging device in front of the locking holes, and decreases the exposure to radiation of the patient and medical team. A 3-D model of the distal nail and of its locking holes was constructed from a pair of calibrated fluoroscopic views. Prior to this, the contours of the nail and locking holes projections had to be determined. A 3-D optical localizer allowed the tracking of reference frames fixed to the nail, imaging device, and drilling motor. A navigation system based on the model guided the surgeon during distal targeting. The robustness, accuracy, and duration of the technique were evaluated in laboratory. The range of acceptable orientations of the X-ray beam has also been determined. Twenty drilling tests were carried out on sawbones. The accuracy and the duration required by our system to perform the distal targeting shows potential suitability for clinical use. The drill passed through the nail locking holes for all of them. The accuracy was about 1.5 mm in translation and 1 degree in rotation. The total time spent on drilling did not exceed 15 min. The system was also assessed in vivo on three patients. | 18,779,062 |
Sparsity-enforced slice-selective MRI RF excitation pulse design. | We introduce a novel algorithm for the design of fast slice-selective spatially-tailored magnetic resonance imaging (MRI) excitation pulses. This method, based on sparse approximation theory, uses a second-order cone optimization to place and modulate a small number of slice-selective sinc-like radio-frequency (RF) pulse segments ("spokes") in excitation k-space, enforcing sparsity on the number of spokes allowed while simultaneously encouraging those that remain to be placed and modulated in a way that best forms a user-defined in-plane target magnetization. Pulses are designed to mitigate B(1) inhomogeneity in a water phantom at 7 T and to produce highly-structured excitations in an oil phantom on an eight-channel parallel excitation system at 3 T. In each experiment, pulses generated by the sparsity-enforced method outperform those created via conventional Fourier-based techniques, e.g., when attempting to produce a uniform magnetization in the presence of severe B(1) inhomogeneity, a 5.7-ms 15-spoke pulse generated by the sparsity-enforced method produces an excitation with 1.28 times lower root mean square error than conventionally-designed 15-spoke pulses. To achieve this same level of uniformity, the conventional methods need to use 29-spoke pulses that are 7.8 ms long. | 18,779,063 |
Continuous and discrete data rebinning in time-of-flight PET. | This paper investigates data compression methods for time-of-flight (TOF) positron emission tomography (PET), which rebin the 3-D TOF measurements into a set of 2-D TOF data for a stack of transaxial slices. The goal of this work is to develop rebinning algorithms that are more accurate than the TOF single-slice-rebinning (TOF-SSRB) method proposed by Mullani in 1982. Two approaches are explored. The first one is based on a partial differential equation, which expresses a consistency condition for TOF-PET data with a Gaussian TOF profile. From this equation we derive an analytical rebinning algorithm, which is unbiased in the limit of continuous sampling. The second approach is discrete: each 2-D rebinned data sample is calculated as a linear combination of the 3-D TOF samples in the same axial plane parallel to the axis of the scanner. The coefficients of the linear combination are precomputed by optimizing a cost function which enforces both accuracy and good variance reduction, models the TOF profile, the axial PSF of the LORs, and the specific sampling scheme of the scanner. Measurements of a thorax phantom on a prototype TOF-PET scanner with a resolution of 550 ps show that the proposed discrete method improves the bias-variance trade-off and is a promising alternative to TOF-SSRB when data compression is required to achieve clinically acceptable reconstruction time. | 18,779,067 |
A healthcare integration system for disease assessment and safety monitoring of dementia patients. | Elderly dementia patients often get lost due to lack of a sense of direction. This may put them at risk and cause their families much worry. The goal of this study is to use information technology to enhance the professional judgment of caregivers, strengthen internal safety monitoring at care organizations, and improve the quality of care for dementia patients. An eXtensible-Markup-Language-based dementia assessment system combining program code and assessment content is used to provide caregivers with better flexibility and real-time response ability. Beyond establishing long-term case files, the system can also perform data consistency analysis, strengthen caregivers' continuing education, improve caregivers' case judgment skills, and reduce the incidence of accidents due to neglect. This study also applies radio frequency identification (RFID) technology to the development of an indoor and outdoor active safety monitoring mechanism. The system can automatically remind caregivers whenever an elderly person approaches a dangerous area or strays too far. Apart from the use of different size tags, the realization of the system also employs the tame transformation signatures (TTS) algorithm to encrypt tag IDs and protect personal privacy. Clinical testing of the system showed that the indoor RFID reader has a response time of 0.5 s when sensing 40 tags, while the outdoor reader has a sensing time of approximately 5 s due to the need to save power. In the latter case, the system can ensure that elderly patients stay less than 15 m away from their caregivers. Patients were relatively willing to wear light tags. We also found that irritable patients with strong mobility were less compliant and often removed their own tags. Caregivers must provide active care and adopt various safety measures to protect the type of patients. | 18,779,072 |
A generic framework for internet-based interactive applications of high-resolution 3-D medical image data. | With the advances in medical imaging devices, large volumes of high-resolution 3-D medical image data have been produced. These high-resolution 3-D data are very large in size, and severely stress storage systems and networks. Most existing Internet-based 3-D medical image interactive applications therefore deal with only low- or medium-resolution image data. While it is possible to download the whole 3-D high-resolution image data from the server and perform the image visualization and analysis at the client site, such an alternative is infeasible when the high-resolution data are very large, and many users concurrently access the server. In this paper, we propose a novel framework for Internet-based interactive applications of high-resolution 3-D medical image data. Specifically, we first partition the whole 3-D data into buckets, remove the duplicate buckets, and then, compress each bucket separately. We also propose an index structure for these buckets to efficiently support typical queries such as 3-D slicer and region of interest, and only the relevant buckets are transmitted instead of the whole high-resolution 3-D medical image data. Furthermore, in order to better support concurrent accesses and to improve the average response time, we also propose techniques for efficient query processing, incremental transmission, and client sharing. Our experimental study in simulated and realistic environments indicates that the proposed framework can significantly reduce storage and communication requirements, and can enable real-time interaction with remote high-resolution 3-D medical image data for many concurrent users. | 18,779,076 |
The effects of cell sizes, environmental conditions, and growth phases on the strength of individual W303 yeast cells inside ESEM. | We performed in situ measurements of mechanical properties of individual W303 wild-type yeast cells by using an integrated environmental scanning electron microscope (ESEM)-nanomanipulator system. Compression experiments to penetrate the cell walls of single cells of different cell sizes (about 3-6 micro m diameter), environmental conditions (600 Pa and 3 mPa), and growth phases (early log, mid log, late log and saturation) were conducted. The compression experiments were performed inside ESEM, embedded with a 7 DOF nanomanipulator with a sharp pyramidal end effector and a cooling stage, i.e., a temperature controller. ESEM itself can control the chamber pressure. Data clearly show an increment in penetration force, i.e., 96 +/- 2, 124 +/- 10, 163 +/- 1, and 234 +/- 14 nN at 3, 4, 5, and 6 micro m cell diameters, respectively. Whereas, 20-fold increase in penetration forces was recorded at different environmental conditions for 5 micro m cell diameter, i.e., 163 +/- 1 nN and 2.95 +/- 0.23 mu N at 600 Pa (ESEM mode) and 3 mPa (HV mode), respectively. This was further confirmed from quantitative estimation of average cell rigidity through the Hertz model, i.e., ESEM mode (3.31 +/- 0.11 MPa) and HV mode (26.02 +/- 3.66 MPa) for 5 micro m cell diameter. Finally, the penetration forces at different cell growth phases also show the increment pattern from log (early, mid, and late) to saturation phases, i.e., 161 +/- 25, 216 +/- 15, 255 +/- 21, and 408 +/- 41 nN, respectively. | 18,779,098 |
[Advance in human free circulating DNA]. | Free circulating DNA is one kind of extracellular free DNA, which was examined in the zoology, botany and the human's body fluid. The detection of free circulating DNA had already been applied in monitoring the disease, embryo's pre-natal diagnosis, tumor research. This article reviewed some biology characteristics of free circulating DNA, the recent researches of free circulating DNA and its application. | 18,779,122 |
[Genetic diversity of Mongolian gerbils (Meriones unguiculatus)]. | Genetic diversity of Z:ZCLA Mongolian gerbils, wild Mongolian gerbils and 3 inbred M. gerbil strains was evaluated with 17 microsatellite loci. The genetic variabilities within and between populations were estimated. The results showed that 9 microsatellite DNA, AF200940, AF200941, AF200942, AF200945, AF200946, AF200947, D11Mit128, PKC, and SCN, were amplified efficiently both in Z:ZCLA M. gerbils and the wild M. gerbils. Forty-one alleles were amplified with the number of alleles per locus ranging from 1 to 7. The average expected heterozygosity (He) and polymorphism information content (PIC) of all the loci were 0.5032 and 0.4656, respectively. The mean effective allele number of Z:ZCLA M. gerbils and wild M. gerbils were 2.78 and 2.89. The PIC of Z:ZCLA M. gerbils and the wild M. gerbils were 0.3704 and 0.3893. In the 3 inbred M. gerbils strains, 8 microsatellite DNA were amplified efficiently with 11 alleles. It displayed heterozygosity in AF200941, AF200945, AF200946, D11Mit128, and SCN loci with fragment lengths from 140 to 215 bp; and homozygosity in AF200942, AF200946, and AF200947 with fragment lengths from 203 to 241 bp. All of the 8 microsatellite loci were monomorphic both within and among the strains. These results suggested that the moderate genetic diversity of the conventional closed colony of Z:ZCLA M. gerbils was observed; and inbred M. gerbils strains basically met the re-quest. Microsatellite markers can be used in monitoring of M. gerbils populations. | 18,779,131 |
[Genetic effects of MC4R and POU1F1 gene on the growth performance in Jinghai yellow chicken]. | Melanocortin-4 receptor (MC4R) gene and pituitary specific transcription factor 1 (POU1F1) gene were studied as candidate genes on the Jinghai yellow chicken in this study. Polymorphisms of MC4R and POU1F1 gene had been analyzed by PCR-SSCP and DNA sequencing method. The relationship between two candidate genes and the growth performance of Jinghai yellow chicken had also been analyzed by GLM model. The frequency of A/B alleles for MC4R gene in the population was 0.929 and 0.071, and that of C/D alleles for POU1F1 gene was 0.500 and 0.500. The results showed that AA genotype of MC4R gene had higher bodyweight at 4, 8, 12 weeks compared to AB and BB genotype (P<0.05); CD genotype of POU1F1 gene had significantly higher bodyweight at all weeks compared to CC and DD genotype (P<0.01). So, it could be preliminarily deduced that MC4R and POU1F1 gene were probably the major gene on growth performance or a QTL linked gene which associated with growth performance in chicken. | 18,779,134 |
[Polymorphisms of mitochondrial Cyt b gene and D-loop region in sweetfish (Plecoglossus altivelis Temminck et Schlegel) from Zhejiang and Fujian Provinces]. | We reported here the molecular analysis of mitochondrial genomes in sweetfish (Plecoglossus altivelis). Thirty-one specimens were recruited from Ruian, Zhejiang Province, Ningde, Fujian Province, and Dongzhang reservoir, Fujian Province. DNA segments spanning cytochrome b gene and D-loop region derived from these specimens were PCR-amplified and subsequently characterized by direct DNA sequence analysis. The resultant sequence data were compared with the consensus sequence and further analyzed for proportion of each nucleotide. The average A, T, C, and G con-tents in Cyt b gene were 19.72%, 29.71%, 32.25%, and 18.32%, respectively, while the contents of A+T and G+C were 49.43% and 50.57%. In the D-loop region, the average A, T, C and G contents were 29.99%, 29.29%, 23.80%, and 16.92% and the contents of A+T and G+C were 59.28% and 40.72%, respectively. There was only one variant in the Cyt b gene belong to two haplotypes and the nucleotide diversity (pi) was merely 0.00028. In the D-loop region, there were only 5 polymorphic sites belonging to 5 haplotypes and its nucleotide diversity (pi) was only 0.00199. These results showed that the genetic diversity of P. altivelis from these regions was very low. | 18,779,137 |
[Development and application of EST-derived SSR markers for bananas (Musa nana Lour.)]. | A total of 2,284 banana unigene sequences were mined, resulting in the identification of 122 SSRs in 110 sequences. Among them, there were 37 motifs the overall average length of SSRs was 20 bp. The trinucleotide repeats appeared to be the most abundant SSRs (47.6%), followed by dinucleotide repeats (33.1%), whereas the tetranucleotide repeats were less abundant. The rich repeats AG and AGG were predominant, accounting for 75.7% and 36% in dri- and tri-nucleotide repeats respectively. A total of 63 primer pairs were designed and tested against genomic DNA of Brazil. Forty-one primers could be validated as usable markers. Nineteen of these primers revealed moderate to high polymorphism information content (PIC) across 49 accessions. The polymorphic bands were ranged from 4 to 12, averagely 7.58. The mean PIC value was 0.7324, ranging from 0.3572 to 0.8744. Forty-nine banana varieties were separated into two major clusters closely corresponding with the genome composition by UPGMA analysis. The results showed that the EST-SSR markers were of great value in evaluation of banana germplasms. | 18,779,139 |
[A girl with partial monosomy 18q21: cytogenetic and molecular genetics studies]. | This study is about a girl with chromosome deletion of 18q and with mental retardation and mild delay of physical development. Based on karyotyping of high resolution, fluorescence in situ hybridization (FISH) and microsatellite analysis mapping to 18q, we found that the patient's karyotype was interpreted as 46,XX,del(18).(pter-->q21:), ish del(18)(D18Z1+,qter-). Detection of D18S979 showed that the region from 18q21.1 to 18qter was deleted, which was originated from her father. There were MBP gene and GALNR gene in the deleted interval in which both of them were lost. In conclusion, deletion of 18q21-->qter including the MBP gene and GALNR gene should be responsible for her mental retardation and mild delay of development. | 18,779,147 |
[Mapping of the yellow inhibitor gene I in silkworm Bombyx mori using SSR markers]. | The yellow color of silkworm (Bombyx mori) cocoon is mainly controlled by three genes, Y (yellow blood), I (yellow inhibitor) and C (out-layer yellow cocoon) genes. I gene locates on the 9th chromosome of silkworm and prevents the transport of carotenoid from epithelia of midgut into hemolymph. Owning to a lack of crossing over in females, reciprocal backcrossed F1(BC1) progenies were used for linkage analysis and mapping of the I gene based on the SSR linkage map using silkworm strains Baghdad (Ba), which express white hemolymph (II+Y+Y), and KY, which express yellow hemolymph (+I+IYY). The gene of interest was linked to three (S0904, S0905, and S0906) SSR markers. All the individuals with white hemolymph in the BC1F (BC1 was generated using F1 as female) showed heterozygous profile of (BaxKY) F1, and the yellow ones in BC1F showed the homozygous profile of the strain KY. Using a reciprocal BC1M cross, we con-structed a linkage map of 38.4 cM, and the distance between I gene and the nearest marker S0904 is 7.4 cM. | 18,779,155 |
[The study on inhabiting endothelial cell aging by targeted silencing of p22phox]. | The aim of the study was to determine the importance and possible mechanism of NAD (P)H oxidase subunits P (superscript 22phox) involved in human umbilical endothelial cell lines ECV-304 aging by special short interference RNA (siRNA). Three siRNAs targeting p22phox were designed and synthesized in vitro, which were used to transfect ECV-304 cultured in vitro for selecting the most powerful and most suitable transfection concentration and time. The cell line ECV-304 was divided into three groups: control group, angiotensin II (Ang II) group, siRNA group, and Ang II + siRNA group. Cell aging was identified by beta-gal stain. Reactive oxygen species (ROS) and NO level in cells and medium were measured. RT-PCR and Western blot were used to analyze mRNA and protein expression of NAD(P)H oxidase subunit p22phox. Among the 3 siRNAs, siRNA-1 was the most powerful on gene silence with 50 nmol/L transfection concentration at 24 h and 36 h. The number of positive cells stained by beta-gal were increased in ECV-304 stimulated with Ang II, and p22phox mRNA and protein expression were increased in aging ECV-304 stimulated with Ang II, which had lower NO and higher ROS. Compared with Ang II group, ROS level was decreased and NO level was increased in Ang+siRNA group with decreased aging level. The result of the present study suggested that siRNA could induce NAD(P)H oxidase subunit p22phox gene silence, Ang II could induce ECV-304 aging cultured in vitro, and the possible pathway of endothelial cell aging is that Ang II upregulates p22phox expression, and then enhances the cell ROS level. | 18,779,176 |
[Integrating genetic and gene expression data: methods and applications of eQTL mapping]. | The availability of high-throughput genotyping technologies and microarray assays has allowed researchers to investigate genetic variations that influence levels of gene expression. Expression Quantitative Trait Locus (eQTL) mapping methods have been used to identify the genetic basis of gene expression. Similar to traditional QTL studies, the main goal of eQTL is to identify the genomic locations to which the expression traits are linked. Although microarrays provide the expression data of thousands of transcripts, standard QTL mapping methods, which are able to handle at most tens of traits, cannot be applied directly. As a result, it is necessary to consider the statistical principles involved in the design and analysis of these experiments. In this paper, we reviewed individual selection, experimental design of microarray, normalization of gene expression data, mapping methods, and explaining of results and proposed potential methodological problems for such analyses. Finally, we discussed the applications of this integrative genomic approach to estimate heritability of transcripts, identify candidate genes, construct gene networks, and understand interactions between genes, genes and environments. | 18,779,184 |
Diagnosis and management of work-related asthma: American College Of Chest Physicians Consensus Statement. | A previous American College of Chest Physicians Consensus Statement on asthma in the workplace was published in 1995. The current Consensus Statement updates the previous one based on additional research that has been published since then, including findings relevant to preventive measures and work-exacerbated asthma (WEA). A panel of experts, including allergists, pulmonologists, and occupational medicine physicians, was convened to develop this Consensus Document on the diagnosis and management of work-related asthma (WRA), based in part on a systematic review, that was performed by the University of Alberta/Capital Health Evidence-Based Practice and was supplemented by additional published studies to 2007. The Consensus Document defined WRA to include occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and WEA (ie, preexisting or concurrent asthma worsened by work factors). The Consensus Document focuses on the diagnosis and management of WRA (including diagnostic tests, and work and compensation issues), as well as preventive measures. WRA should be considered in all individuals with new-onset or worsening asthma, and a careful occupational history should be obtained. Diagnostic tests such as serial peak flow recordings, methacholine challenge tests, immunologic tests, and specific inhalation challenge tests (if available), can increase diagnostic certainty. Since the prognosis is better with early diagnosis and appropriate intervention, effective preventive measures for other workers with exposure should be addressed. The substantial prevalence of WRA supports consideration of the diagnosis in all who present with new-onset or worsening asthma, followed by appropriate investigations and intervention including consideration of other exposed workers. | 18,779,187 |
Surfactant protein D and bronchial dysplasia in smokers at high risk of lung cancer. | Surfactant dysfunction has been implicated in both lung cancer and COPD. This study evaluated the relationship between surfactant protein D (SP-D) and the progression of bronchial dysplasia in heavy smokers. SP-D and oxidized glutathione levels were determined in samples of BAL fluid from 71 ex-smokers and current heavy smokers who participated in a lung cancer chemoprevention study with inhaled budesonide therapy. Bronchoscopy with biopsies was performed at baseline and was repeated at 6 months. The primary end point was the progression of bronchial dysplasia over 6 months. Log-normalized SP-D levels in BAL fluid were significantly associated with the progression of bronchial dysplasia. A 1-U decrease in log-normalized SP-D levels at baseline was associated with a 3.2-fold increase (95% confidence interval, 1.24 to 8.26) in the risk for progression. Reduced FEV(1) also predicted the progression of bronchial dysplasia (p < 0.05). Additional reductions in BAL fluid SP-D levels over the 6 months further increased the risk of progression (odds ratio, 1.76 for a 1-U decrease in log-normalized SP-D levels in BAL fluid; p = 0.023). Thirty-seven percent of the variation in SP-D levels in BAL fluid was related positively to the subject's FEV(1)/FVC ratio, and inversely to their plasma C-reactive protein levels and number of pack-years of smoking. Reduced SP-D expression in BAL fluid was associated with the progression of bronchial dysplasia. SP-D levels in BAL fluid may serve as a potential biomarker to identify smokers who are at risk of early lung cancer. | 18,779,194 |
Dementia prevention: methodological explanations for inconsistent results. | The prevention of neurodegenerative dementias, such as Alzheimer disease, is a growing public health concern, because of a lack of effective curative treatment options and a rising global prevalence. Various potential risk or preventive factors have been suggested by epidemiologic research, including modifiable lifestyle factors, such as social contacts, leisure activities, physical exercise, and diet, as well as some preventive pharmacologic strategies, such as hormone replacement therapy, nonsteroidal antiinflammatory drugs, and Ginkgo biloba. Some factors have been targeted by interventions tested in randomized controlled trials, but many of the results are in conflict with observational evidence. The aim of this paper is to review the epidemiologic data linking potential protective factors to dementia or cognitive decline and to discuss the methodological limitations that could explain conflicting results. A thorough review of the literature suggests that, even if there are consistent findings from large observational studies regarding preventive or risk factors for dementia, few randomized controlled trials have been designed specifically to prove the protective effects of interventions based on such factors on dementia incidence. Because of the multifactorial origin of dementia, it appears that multidomain interventions could be a suitable candidate for preventive interventions, but designing such trials remains very challenging for researchers. | 18,779,228 |
Continuous glucose monitoring and intensive treatment of type 1 diabetes. | The value of continuous glucose monitoring in the management of type 1 diabetes mellitus has not been determined. In a multicenter clinical trial, we randomly assigned 322 adults and children who were already receiving intensive therapy for type 1 diabetes to a group with continuous glucose monitoring or to a control group performing home monitoring with a blood glucose meter. All the patients were stratified into three groups according to age and had a glycated hemoglobin level of 7.0 to 10.0%. The primary outcome was the change in the glycated hemoglobin level at 26 weeks. The changes in glycated hemoglobin levels in the two study groups varied markedly according to age group (P=0.003), with a significant difference among patients 25 years of age or older that favored the continuous-monitoring group (mean difference in change, -0.53%; 95% confidence interval [CI], -0.71 to -0.35; P<0.001). The between-group difference was not significant among those who were 15 to 24 years of age (mean difference, 0.08; 95% CI, -0.17 to 0.33; P=0.52) or among those who were 8 to 14 years of age (mean difference, -0.13; 95% CI, -0.38 to 0.11; P=0.29). Secondary glycated hemoglobin outcomes were better in the continuous-monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the two study groups; however, the trial was not powered to detect such a difference. Continuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes. Further work is needed to identify barriers to effectiveness of continuous monitoring in children and adolescents. (ClinicalTrials.gov number, NCT00406133.) | 18,779,236 |
UK epidemic Escherichia coli strains A-E, with CTX-M-15 beta-lactamase, all belong to the international O25:H4-ST131 clone. | Uropathogenic and invasive Escherichia coli O25:H4-ST131 isolates producing CTX-M-15 extended-spectrum beta-lactamase (ESBL) enzymes have recently been shown to be disseminated across the globe. In the UK, many CTX-M-15 ESBL-producing E. coli strains have been previously defined as belonging to the epidemic strains A-E, as determined by PFGE. The present study was carried out to define the relationship between these two groups of pathogenic E. coli. Multilocus sequence typing and PFGE were used for molecular characterization of a collection of 61 ESBL-producing E. coli isolates from across the UK. Strains A to E all belonged to the ST131 clone, further underscoring the epidemiological importance of this lineage. The future spread of the ST131 clone, and its UK variants, should be monitored closely and the pathogenic mechanisms explaining their success should be investigated. | 18,779,256 |
Association between non-subcutaneous adiposity and calcified coronary plaque: a substudy of the Multi-Ethnic Study of Atherosclerosis. | Excessive non-subcutaneous fat deposition may impair the functions of surrounding tissues and organs through the release of inflammatory cytokines and free fatty acids. We examined the cross-sectional association between non-subcutaneous adiposity and calcified coronary plaque, a noninvasive measure of coronary artery disease burden. Participants in the Multi-Ethnic Study of Atherosclerosis underwent computed tomography (CT) assessment of calcified coronary plaque. We measured multiple fat depots in 398 white and black participants (47% men, 43% black), aged 47-86 y, from Forsyth County, NC, during 2002-2005, with the use of cardiac and abdominal CT scans. In addition to examining each depot separately, we also created a non-subcutaneous fat index with the standard scores of non-subcutaneous fat depots. A total of 219 participants (55%) were found to have calcified coronary plaque. After adjusting for demographics, lifestyle factors, and height, calcified coronary plaque was associated with a 1 SD increment in the non-subcutaneous fat index [odds ratio (OR): 1.41; 95% CI: 1.08, 1.84], pericardial fat (OR: 1.38; 95% CI: 1.04, 1.84), abdominal visceral fat (OR: 1.35; 95% CI: 1.03, 1.76) but not with fat content in the liver, intermuscular fat, or abdominal subcutaneous fat. The relation between non-subcutaneous fat index and calcified coronary plaque remained after further adjustment for abdominal subcutaneous fat (OR: 1.40; 95% CI: 1.00, 1.94). The relation did not differ by sex and ethnicity. The overall burden of non-subcutaneous fat deposition, but not abdominal subcutaneous fat, may be a correlate of coronary atherosclerosis. | 18,779,279 |
Present situation of biomarkers for copper status. | Serum or plasma copper and ceruloplasmin concentrations are the most widely used laboratory indicators to evaluate copper status. Both indicators are decreased in moderate or severe copper deficiency. The activity of several cuproenzymes is decreased in mild copper deficiency. However, their use is limited by the nonexistence of standardized assays and high interindividual variability and because some of these indicators are affected by other conditions. Recently, it was shown that the protein expression of the copper chaperone for superoxide dismutase (CCS) is increased in erythrocytes of rodents with mild copper deficiency. However, no traditional laboratory indicators have been identified as potential early markers of copper excess. It is possible that the biomarkers studied so far are not sensitive enough to detect an increase in body copper before the appearance of functional or clinical effects or that the homeostatic mechanisms are so strong that no significant changes in body copper occur with mild-to-moderate copper exposure. The identification of appropriate biomarkers for early detection of an increase in body copper represents a major challenge for further research, and the development of new approaches, such as network biology, allows us to search and propose new candidates to be studied. Recently, we found that CCS mRNA abundance in mononuclear blood cells significantly decreased after copper supplementation. The usefulness of this indicator to detect an increase in body copper should be assessed in clinical trials. | 18,779,309 |
The ING4 tumor suppressor attenuates NF-kappaB activity at the promoters of target genes. | The NF-kappaB family mediates immune and inflammatory responses. In many cancers, NF-kappaB is constitutively activated and induces the expression of genes that facilitate tumorigenesis. ING4 is a tumor suppressor that is absent or mutated in several cancers. Herein, we demonstrate that in human gliomas, NF-kappaB is constitutively activated, ING4 expression is negligible, and NF-kappaB-regulated gene expression is elevated. We demonstrate that an ING4 and NF-kappaB interaction exists but does not prevent NF-kappaB activation, nuclear translocation, or DNA binding. Instead, ING4 and NF-kappaB bind simultaneously at NF-kappaB-regulated promoters, and this binding correlates with reductions in p65 phosphorylation, p300, and the levels of acetylated histones and H3-Me3K4, while enhancing the levels of HDAC-1 at these promoters. Using a knockdown approach, we correlate reductions in ING4 protein levels with increased basal and inducible NF-kappaB target gene expression. Collectively, these data suggest that ING4 may specifically regulate the activity of NF-kappaB molecules that are bound to target gene promoters. | 18,779,315 |
Paradoxical effect of mitochondrial respiratory chain impairment on insulin signaling and glucose transport in adipose cells. | Adipocyte function is crucial for the control of whole body energy homeostasis. Pathway analysis of differentiating 3T3-L1 adipocytes reveals that major metabolic pathways induced during differentiation involve mitochondrial function. However, it is not clear why differentiated white adipocytes require enhanced respiratory chain activity relative to pre-adipocytes. To address this question, we used small interference RNA to interfere with the induction of the transcription factor Tfam, which is highly induced between days 2 and 4 of differentiation and is crucial for replication of mitochondrial DNA. Interference with Tfam resulted in cells with decreased respiratory chain capacity, reflected by decreased basal oxygen consumption, and decreased mitochondrial ATP synthesis, but no difference in many other adipocyte functions or expression levels of adipose-specific genes. However, insulin-stimulated GLUT4 translocation to the cell surface and subsequent glucose transport are impaired in Tfam knockdown cells. Paradoxically, insulin-stimulated Akt phosphorylation is significantly enhanced in these cells. These studies reveal independent links between mitochondrial function, insulin signaling, and glucose transport, in which impaired respiratory chain activity enhances insulin signaling to Akt phosphorylation, but impairs GLUT4 translocation. These results indicate that mitochondrial respiratory chain dysfunction in adipocytes can cause impaired insulin responsiveness of GLUT4 translocation by a mechanism downstream of the Akt protein kinase. | 18,779,333 |
Recruitment of Rab27a to phagosomes controls microbial antigen cross-presentation by dendritic cells. | Polyreactive immunoglobulins (Ig) and complement components are present in tissues and blood of healthy individuals. They facilitate pathogen uptake and inactivation in lysosomes of phagocytes and thereby provide rapid protection against infection. Dendritic cells (DCs) are phagocytes that can acquire peptides from phagocytosed antigen to elicit cytotoxic immune responses by CD8(+) T lymphocytes. The mechanisms that select peptides for cross-presentation are not fully resolved. Here we investigated the role of polyreactive Ig and complement in directing phagosomal antigen processing for cross-presentation. Phagocytosis facilitated by serum opsonization required the presence of Ig for effective antigen cross-presentation of microbe-derived antigen. The presence of complement C3 in serum promoted phagocytosis, yet phagosomes were defective in antigen degradation. The small GTPase Rab27a was recently implicated in antigen cross-presentation and was rapidly recruited to phagosomes only when Ig was present. Our data suggest that prebinding of antigen by polyreactive Ig potentiates the efficiency of antigen cross-presentation to CD8(+) T cells through recruitment of Rab27a. | 18,779,337 |
Functional characterization and novel rickettsiostatic effects of a Kunitz-type serine protease inhibitor from the tick Dermacentor variabilis. | Here we report the novel bacteriostatic function of a five-domain Kunitz-type serine protease inhibitor (KPI) from the tick Dermacentor variabilis. As ticks feed, they release anticoagulants, anti-inflammatory and immunosuppressive molecules that mediate the formation of the feeding lesion on the mammalian host. A number of KPIs have been isolated and characterized from tick salivary gland extracts. Interestingly, we observe little D. variabilis KPI gene expression in the salivary gland and abundant expression in the midgut. However, our demonstration of D. variabilis KPI's anticoagulant properties indicates that D. variabilis KPI may be important for blood meal digestion in the midgut. In addition to facilitating long-term attachment and blood meal acquisition, gene expression studies of Drosophila, legumes, and ticks suggest that KPIs play some role in the response to microbial infection. Similarly, in this study, we show that challenge of D. variabilis with the spotted fever group rickettsia, Rickettsia montanensis, results in sustained D. variabilis KPI gene expression in the midgut. Furthermore, our in vitro studies show that D. variabilis KPI limits rickettsial colonization of L929 cells (mouse fibroblasts), implicating D. variabilis KPI as a bacteriostatic protein, a property that may be related to D. variabilis KPI's trypsin inhibitory capability. This work suggests that anticoagulants play some role in the midgut during feeding and that D. variabilis KPI may be involved as part of the tick's defense response to rickettsiae. | 18,779,339 |
Efficacy of the combination of tachyplesin III and clarithromycin in rat models of Escherichia coli sepsis. | We investigated the efficacy of tachyplesin III and clarithromycin in two experimental rat models of severe gram-negative bacterial infections. Adult male Wistar rats were given either (i) an intraperitoneal injection of 1 mg/kg Escherichia coli 0111:B4 lipopolysaccharide or (ii) 2 x 10(10) CFU of E. coli ATCC 25922. For each model, the animals received isotonic sodium chloride solution, 1 mg/kg tachyplesin III, 50 mg/kg clarithromycin, or 1 mg/kg tachyplesin III combined with 50 mg/kg clarithromycin intraperitoneally. Lethality, bacterial growth in the blood and peritoneum, and the concentrations of endotoxin and tumor necrosis factor alpha (TNF-alpha) in plasma were evaluated. All the compounds reduced the lethality of the infections compared to that for the controls. Tachyplesin III exerted a strong antimicrobial activity and achieved a significant reduction of endotoxin and TNF-alpha concentrations in plasma compared to those of the control and clarithromycin-treated groups. Clarithromycin exhibited no antimicrobial activity but had a good impact on endotoxin and TNF-alpha plasma concentrations. A combination of tachyplesin III and clarithromycin resulted in significant reductions in bacterial counts and proved to be the most-effective treatment in reducing all variables measured. | 18,779,356 |
The mouth of a dense-core vesicle opens and closes in a concerted action regulated by calcium and amphiphysin. | Secretion of hormones and peptides by neuroendocrine cells occurs through fast and slow modes of vesicle fusion but the mechanics of these processes are not understood. We used interference reflection microscopy to monitor deformations of the membrane surface and found that both modes of fusion involve the tightly coupled dilation and constriction of the vesicle. The rate of opening is calcium dependent and occurs rapidly at concentrations <5 muM [corrected] The fast mode of fusion is blocked selectively by a truncation mutant of amphiphysin. Vesicles do not collapse when fusion is triggered by strontium, rather they remain locked open and membrane scission is blocked. In contrast, constriction of the vesicle opening continues when endocytosis is blocked by inhibiting the function of dynamin. Thus, fast and slow modes of fusion involve similar membrane deformations and vesicle closure can be uncoupled from membrane scission. Regulation of these processes by calcium and amphiphysin may provide a mechanism for controlling the release of vesicle contents. | 18,779,374 |
Time-dependent block of ultrarapid-delayed rectifier K+ currents by aconitine, a potent cardiotoxin, in heart-derived H9c2 myoblasts and in neonatal rat ventricular myocytes. | Aconitine (ACO), a highly toxic diterpenoid alkaloid, is recognized to have effects on cardiac voltage-gated Na(+) channels. However, it remains unknown whether it has any effects on K(+) currents. The effects of ACO on ion currents in differentiated clonal cardiac (H9c2) cells and in cultured neonatal rat ventricular myocytes were investigated in this study. In H9c2 cells, ACO suppressed ultrarapid-delayed rectifier K(+) current (I(Kur)) in a time- and concentration-dependent fashion. The IC(50) value for ACO-induced inhibition of I(Kur) was 1.4 microM. ACO could accelerate the inactivation of I(Kur) with no change in the activation time constant of this current. Steady-state inactivation curve of I(Kur) during exposure to ACO could be demonstrated. Recovery from block by ACO was fitted by a single-exponential function. The inhibition of I(Kur) by ACO could still be observed in H9c2 cells preincubated with ruthenium red (30 microM). Intracellular dialysis with ACO (30 microM) had no effects on I(Kur). I(Kur) elicited by simulated action potential (AP) waveforms was sensitive to block by ACO. Single-cell Ca(2+) imaging revealed that ACO (10 microM) alone did not affect intracellular Ca(2+) in H9c2 cells. In cultured neonatal rat ventricular myocytes, ACO also blocked I(Kur) and prolonged AP along with appearance of early afterdepolarizations. Multielectrode recordings on neonatal rat ventricular tissues also suggested that ACO-induced electrocardiographic changes could be associated with inhibition of I(Kur). This study provides the evidence that ACO can produce a depressant action on I(Kur) in cardiac myocytes. | 18,779,382 |
The protein and the gene encoding the receptor for the cellular uptake of transcobalamin-bound cobalamin. | The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC- cobalamin (Cbl) and internalizes the complex by endocytosis. This receptor was purified from human placental membranes by affinity chromatography. Tryptic digest of the protein extracted from a sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel and subjected to liquid chromatography/mass spectrometry identified 4 peptides that matched with a membrane protein in the data bank. TCblR belongs to the low-density lipoprotein receptor family, with 2 low-density lipoprotein receptor type A domains separated by a complement-like cysteine-rich region. The 282-amino acid sequence includes a signal peptide of 31 residues, extracellular domain of 198 residues, a transmembrane region of 21 residues, and a cytoplasmic domain of 32 residues. The binding of TC-Cbl does not require the cytoplasmic domain or its orientation in the plasma membrane because the recombinant extracellular domain binds TC-Cbl with high affinity and specificity. The protein is heavily glycosylated and accounts for the 58-kDa size by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The human gene first identified as 8D6A and more recently as CD 320 encoding TCblR is located at p13.2 on the short arm of chromosome 19, spans a length of 6.224 kb, and is composed of 5 exons and 4 introns. | 18,779,389 |
Natural killer T-cell autoreactivity leads to a specialized activation state. | Natural killer T (NKT) cells are innate-like T cells that recognize specific microbial antigens and also display autoreactivity to self-antigens. The nature of NKT-cell autoreactive activation remains poorly understood. We show here that the mitogen-activated protein kinase (MAPK) pathway is operative during human NKT-cell autoreactive activation, but calcium signaling is severely impaired. This results in a response that is biased toward granulocyte macrophage colony-stimulating factor (GM-CSF) secretion because this cytokine requires extracellular signal-regulated kinase (ERK) signaling but is not highly calcium dependent, whereas interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-2 production are minimal. Autoreactive activation was associated with reduced migration velocity but did not induce arrest; thus, NKT cells retained the ability to survey antigen presenting cells (APCs). IL-12 and IL-18 stimulated autoreactively activated NKT cells to secrete IFN-gamma, and this was mediated by Janus kinase-signal transducers and activators of transcription (JAK-STAT)-dependent signaling without induction of calcium flux. This pathway did not require concurrent contact with CD1d(+) APCs but was strictly dependent on preceding autoreactive stimulation that induced ERK activation. In contrast, NKT-cell responses to the glycolipid antigen alpha-galactosyl ceramide (alpha-GalCer) were dampened by prior autoreactive activation. These results show that NKT-cell autoreactivity induces restricted cytokine secretion and leads to altered basal activation that potentiates innate responsiveness to costimulatory cytokines while modulating sensitivity to foreign antigens. | 18,779,390 |
Cardiac involvement in patients with limb-girdle muscular dystrophy type 2 and Becker muscular dystrophy. | To investigate the extent of cardiac involvement in patients with 1 of the 12 groups of recessively inherited limb-girdle muscular dystrophy type 2 (LGMD2A-L) and Becker muscular dystrophy (BMD). Prospective screening. Neuromuscular Clinic and Department of Cardiology at Rigshospitalet. Patients One hundred one patients with LGMD2A-I and BMD and 29 patients with LGMD2 and no molecular diagnosis. Clinical investigation, echocardiography, and electrocardiographic findings. Cardiac involvement was present in 24 of 100 patients (24%) with LGMD2A-I and in 14 of 30 patients (47%) with BMD. Only a few patients with LGMD2A and unclassified LGMD2 had mild cardiac involvement, whereas 29% and 67% of patients with LGMD2I and LGMD2E, respectively, had cardiac involvement. Cardiac involvement was not correlated with age, muscle strength, or the level of dystrophic changes on muscle biopsy. This study demonstrates a high prevalence of cardiac involvement in patients with LGMD2I, LGMD2E, and BMD. Patients with LGMD2A, LGMD2D, and unclassified LGMD2 have a much lower and milder prevalence of cardiac involvement. | 18,779,423 |
Role of the neuropathology of Alzheimer disease in dementia in the oldest-old. | Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the brain, especially in the hippocampus, entorhinal cortex, and isocortex, are hallmark lesions of Alzheimer disease and dementia in the elderly. However, this association has not been extensively studied in the rapidly growing population of the very old. To assess the relationship between estimates of cognitive function and NP and NFT pathologic conditions in 317 autopsied persons aged 60 to 107 years. We studied the relationship between severity of dementia and the density of these characteristic lesions of Alzheimer disease in young-old, middle-old, and oldest-old persons. The relationship of the severity of dementia as measured by the Clinical Dementia Rating scale to the density of NPs and NFTs was then assessed in each age group. Three hundred seventeen brains of persons aged 60 years and older were selected to have either no remarkable neuropathological lesions or only NP and NFT lesions. Brains with any other neuropathological conditions, either alone or in addition to Alzheimer disease findings, were excluded. The study cohort was then stratified into the youngest quartile (aged 60-80 years), middle 2 quartiles (aged 81-89 years), and oldest quartile (aged 90-107 years). While the density of NPs and NFTs rose significantly by more than 10-fold as a function of the severity of dementia in the youngest-old group, significant increases in the densities of NPs and NFTs were absent in the brains of the oldest-old. This lack of difference in the densities of NPs and NFTs was due to reduced lesion densities in the brains of oldest-old persons with dementia rather than to increased density of these lesions in the brains of nondemented oldest-old persons. These findings suggest that the neuropathological features of dementia in the oldest-old are not the same as those of cognitively impaired younger-old persons and compel a vigorous search for neuropathological indices of dementia in this most rapidly growing segment of the elderly population. | 18,779,425 |
Particulate air pollution as a risk factor for ST-segment depression in patients with coronary artery disease. | The association of particulate matter (PM) with cardiovascular morbidity and mortality is well documented. PM-induced ischemia is considered a potential mechanism linking PM to adverse cardiovascular outcomes. In a repeated-measures study including 5979 observations on 48 patients 43 to 75 years of age, we investigated associations of ambient pollution with ST-segment level changes averaged over half-hour periods measured in the modified V(5) position by 24-hour Holter ECG monitoring. Each patient was observed up to 4 times within 1 year after a percutaneous intervention for myocardial infarction, acute coronary syndrome without infarction, or stable coronary artery disease without acute coronary syndrome. Elevation in fine particles (PM(2.5)) and black carbon levels predicted depression of half-hour-averaged ST-segment levels. An interquartile increase in the previous 24-hour mean black carbon level was associated with a 1.50-fold increased risk of ST-segment depression > or =0.1 mm (95% CI, 1.19 to 1.89) and a -0.031-mm (95% CI, -0.042 to -0.019) decrease in half-hour-averaged ST-segment level (continuous outcome). Effects were greatest within the first month after hospitalization and for patients with myocardial infarction during hospitalization or with diabetes. ST-segment depression is associated with increased exposure to PM(2.5) and black carbon in cardiac patients. The risk of pollution-associated ST-segment depression may be greatest in those with myocardial injury in the first month after the cardiac event. | 18,779,445 |
Actigraphy-measured sleep characteristics and risk of falls in older women. | Prior studies have suggested that insomnia and self-reported poor sleep are associated with increased risk of falls. However, no previous study, to our knowledge, has tested the independent associations of objectively estimated characteristics of sleep and risk of falls, accounting for the use of commonly prescribed treatments for insomnia. Study subjects were participants in the Study of Osteoporotic Fractures. In 2978 primarily community-dwelling women 70 years and older (mean age, 84 years), sleep and daytime inactivity were estimated using wrist actigraphy data collected for a minimum of 3 consecutive 24-hour periods (mean duration, 86.3 hours). Fall frequency during the subsequent year was ascertained by a triannual questionnaire. Use of medications was obtained by examiner interview. In multivariate-adjusted models, relative to those with "normal" nighttime sleep duration (>7 to 8 hours per night), the odds of having 2 or more falls in the subsequent year was elevated for women who slept 5 hours or less per night (odds ratio, 1.52; 95% confidence interval, 1.03-2.24). This association was not explained by the use of benzodiazepines. Indexes of sleep fragmentation were also associated with an increased risk of falls. For example, women with poor sleep efficiency (<70% of time in bed spent sleeping) had 1.36-fold increased odds of falling compared with others (odds ratio, 1.36; 95% confidence interval, 1.07-1.74). Short nighttime sleep duration and increased sleep fragmentation are associated with increased risk of falls in older women, independent of benzodiazepine use and other risk factors for falls. | 18,779,464 |
Consensus conference: multimodality management of early- and intermediate-stage non-small cell lung cancer. | Surgery is the mainstay of treatment in early- and intermediate-stage non-small cell lung cancer (NSCLC), yet recurrences are frequent. Studies have documented the benefits of chemotherapy administered after resection, but a number of questions remain regarding how overall outcomes can be further improved. To provide the oncology community with direction on these issues, a consensus conference of leading experts in the NSCLC field was held at the Fifth Annual Atlanta Lung Cancer Symposium on October 25-27, 2007. The available scientific literature is presented and when such literature is lacking, clinical experience is provided to support the following conclusions. Preoperative staging should be done in accordance with the National Comprehensive Cancer Network guidelines, but endoscopic fine needle aspiration of enlarged mediastinal nodes can be used, and if histology is positive for malignancy, mediastinoscopy can be avoided. Neoadjuvant systemic therapy is not generally recommended but can be considered to downstage an unresectable patient. There is currently no role for preoperative radiation or chemoradiation. Adjuvant systemic therapy is not recommended for stage IA and IB patients; however, adverse prognostic factors are acceptable reasons to consider adjuvant systemic therapy in the latter. Adjuvant systemic therapy is recommended for stage IIA, IIB, and IIIA patients, consistent with recent American Society of Clinical Oncology guidelines. A cisplatin-based regimen should be started within 60 days after surgery, but if relatively contraindicated, carboplatin is an acceptable alternative. Adjuvant radiation therapy is not recommended for N0 and N1 patients, but is used in N2 patients to decrease local recurrence. | 18,779,538 |
An intervention for treating alcohol dependence: relating elements of Medical Management to patient outcomes with implications for primary care. | Alcohol dependence, frequently seen in medical settings, is a major problem that affects the health and well-being of many individuals and their families. The purpose of this study was to examine the relationship between treatment outcomes and patient and clinician factors specifically associated with a medically oriented intervention given for the treatment of alcohol dependence. The intervention was developed for the National Institute on Alcohol Abuse and Alcoholism-sponsored COMBINE Study, a randomized controlled trial combining 2 medications, naltrexone and acamprosate, with Medical Management, with or without specialty alcohol treatment. We examined the effect of patient adherence to treatment (number of Medical Management visits, total minutes in treatment, alliance or therapeutic relationship with the clinician, patient satisfaction with treatment, and clinician adherence to the Medical Management protocol) on abstinence from alcohol, amount of heavy drinking, and clinical improvement during treatment. More Medical Management visits attended and less total time spent in Medical Management treatment was associated with more days of abstinence from alcohol, reductions in heavy alcohol drinking, and a higher likelihood of clinical improvement. The patients' positive perceptions of their alliance with their clinician and their satisfaction with treatment was significantly associated with more days of abstinence from alcohol during treatment. Two clinician factors clinician confidence in the Medical Management treatment and flexibility in delivering Medical Management were also associated with better patient outcomes. Medically trained clinicians with minimal specialty training in alcohol dependence treatments were able to deliver a brief and effective medication management intervention that was designed to be consistent with primary care practice. | 18,779,548 |
Peripheral Abeta subspecies as risk biomarkers of Alzheimer's disease. | Plasma Abeta42 and Abeta40 levels are putative biomarkers for Alzheimer's disease (AD), but their significance and predictive value have been inconclusive. In AD transgenic models, plasma and cerebrospinal fluid levels of Abeta42 and Abeta40 increase with age but subsequently decrease when Abeta begins to accumulate in brain and with the onset of cognitive impairment. To determine the predictive value of Abeta levels in elderly populations, we investigated how plasma Abeta42, Abeta40, and a protofibrillar subspecies of Abeta42 changed over time and with the onset of cognitive impairment or AD. In a cohort of 1,125 elderly persons without dementia, 104 (9.2%) of the participants developed AD over 4.6 years of follow-up. Higher plasma Abeta42 levels at the onset of the study were associated with a threefold increased risk of AD. However, conversion to AD was accompanied by a significant decline in plasma Abeta42, a decreased Abeta42/Abeta40 ratio and, with the onset of cognitive impairment, decreased protofibrillar Abeta42 levels. Our results suggest individuals with elevated plasma Abeta42 are at increased risk of AD and that with the onset of disease, the decline in some forms of Abeta may reflect compartmentalization of Abeta peptides in the brain. | 18,779,561 |
Hierarchies of networked phases induced by multiple liquid-liquid critical points. | Nanoparticles and colloids functionalized by four single strands of DNA can be thought of as designed analogs to tetrahedral network-forming atoms and molecules, with a difference that the attached DNA strands allow for control of the length scale of bonding relative to the core size. We explore the behavior of an experimentally realized model for nanoparticles functionalized by four single strands of DNA (a tetramer), and show that this single-component model exhibits a rich phase diagram with at least three critical points and four thermodynamically distinct amorphous phases. We demonstrate that the additional critical points are part of the Ising universality class, like the ordinary liquid-gas critical point. The dense phases consist of a hierarchy of interpenetrating networks, reminiscent of a woven cloth. Thus, bonding specificity of DNA provides an effective route to generate new nano-networked materials with polyamorphic behavior. The concept of network interpenetration helps to explain the generation of multiple liquid phases in single-component systems, suggested to occur in some atomic and molecular network-forming fluids, including water and silica. | 18,779,565 |
Sinusoidal obstructive syndrome diagnosed with superparamagnetic iron oxide-enhanced magnetic resonance imaging in patients with chemotherapy-treated colorectal liver metastases. | To assess the predictive value of superparamagnetic iron oxide (SPIO) -enhanced T2-weighted gradient echo (GRE) imaging to determine the presence and severity of sinusoidal obstructive syndrome (SOS). Sixty hepatic resection patients with colorectal metastases treated with chemotherapy underwent unenhanced magnetic resonance imaging (MRI) followed by T2-weighted GRE sequences obtained after SPIO. The images were reviewed in consensus by two experienced observers who determined the presence and severity of linear and reticular hyperintensities, indicating SOS-type liver injury, using a 4-point ordinal scale. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% CIs for the detection of SOS were calculated. Twenty-four of 60 patients had moderate to severe SOS on MRI. MRI achieved a sensitivity of 87% (95% CI, 66% to 97%), specificity of 89% (95% CI, 75% to 97%), PPV of 83% (95% CI, 63% to 95%), and NPV of 92% (95% CI, 77% to 98%). SOS was never found at surgery or histology in patients whose background liver parenchyma was normal on SPIO-enhanced MRI. SOS is present in a significant proportion of patients with treated colorectal metastases and is effectively detected on SPIO-enhanced T2-weighted GRE images. | 18,779,617 |
Nanofiber applications for burn care. | Nanotechnology is a growing field of manufactured materials with sizes less than 1 mum, and it is particularly useful in the field of medicine because these applications replicate components of a cell's in vivo environment. Nanofibers, which mimic collagen fibrils in the extracellular matrix (ECM), can be created from a host of natural and synthetic compounds and have multiple properties that may be beneficial to burn wound care. These properties include a large surface-area-to-volume ratio, high porosity, improved cell adherence, proliferation and migration, and controlled in vivo degradation rates. The large surface area of nanofiber mats allows for increased interaction with compounds and provides a mechanism for sustained release of antibiotics, analgesics, or growth factors into burn wounds; high porosity allows diffusion of nutrients and waste. Improved cell function on these scaffolds will promote healing. Controlled degradation rates of these scaffolds will promote scaffold absorption after its function is no longer required. The objective of this article is to review the current literature describing nanofibers and their potential application to burn care. | 18,779,672 |
The relationship of self-reported sleep disturbance, mood, and menopause in a community study. | The aim of this study was to assess the relationship between sleep disturbance, mood, menopausal status, and vasomotor symptoms in middle-aged women in Kinmen. A community-based sample of 1,113 Taiwanese women aged 43 to 57 years who were living on the island of Kinmen were recruited in this cross-sectional study. Menopausal status was determined by menstrual history. Sleep quality was measured by self-reported sleep problems. Anxiety and depression were assessed by the Hospital Anxiety Depression Scale. Forty-six percent of middle-aged women reported feeling dissatisfied with their sleep. Total sleep hours were not significantly different as a function of menopausal status. Generally, the occurrence of sleep problems or poor sleep quality was most prevalent in the postmenopausal group and least prevalent in premenopausal women. After analysis by multiple logistic regression, menopausal status was the independent factor of difficulty initiating sleep and sleep fragmentation. The Hospital Anxiety Depression Scale anxiety score was related to all sleep problems except for "excessive daytime sleepiness" and "awakening without further sleep." Almost half of the Taiwanese middle-aged women felt dissatisfied with their sleep. Both menopausal status and higher anxiety score were associated with poor sleep quality of midlife women. | 18,779,680 |
The role of high frequency oscillatory ventilation in the management of children with severe traumatic brain injury and concomitant lung pathology. | To report the use of high frequency oscillatory ventilation (HFOV) in two children with severe traumatic brain injury and concurrent lung pathology where conventional mechanical ventilation was ineffective. : Case report. Regional intensive care unit in a pediatric teaching hospital. Two severely head-injured children (both with postresuscitation Glasgow Coma Scores of 3), one of whom was age 11 yrs and developed an invasive fungal (rhizomucor) pneumonia, while the other age 5 yrs had bilateral lung contusions. Both were treated according to local head injury guidelines, which included conventional ventilation. Despite increasing conventional ventilatory support, CO2 removal became problematic in both cases, making the intracranial pressure control and consequent maintenance of adequate cerebral perfusion pressure difficult. In both patients, a dramatic reduction in intracranial pressure and improvement in cerebral perfusion pressure was observed soon after the use of HFOV. Additionally, inotropic support was weaned by 50% in both children after commencing HFOV. A significant increase in the mean arterial blood pressure occurred in one child with HFOV. Use of HFOV as an alternative to conventional mechanical ventilation. HFOV may have utility in the management of selected cases of severe brain trauma with concurrent lung pathology where conventional ventilation is ineffective. | 18,779,699 |
Peripheral T-cell lymphoma with follicular T-cell markers. | Peripheral T-cell lymphomas (PTCLs) in western countries are uncommon tumors with unfavorable prognosis. They may be subclassified as anaplastic large-cell lymphomas (ALCLs), angioimmunoblastic-T-cell lymphomas (AITLs), or unspecified peripheral T-cell lymphomas (PTCLs-U). It has recently been demonstrated that AITLs originate from germinal center follicular helper T cells (TFH), whereas the normal counterparts of other PTCLs remain essentially unknown. The aim of this study was to establish whether other PTCL subgroups also express TFH cell markers. One hundred forty-six PTCLs were analyzed for programmed death-1 (PD-1) expression in tissue microarrays using a new monoclonal antibody called NAT-105. PD-1-positive cases, which did not fulfill all the criteria for AITL, were further evaluated in whole-tissue sections for another 12 immunohistochemical markers, including the TFH cell markers CXCL13, CD10, and BCL6. Clonal Ig and T-cell receptor rearrangements and Epstein-Barr virus-encoded RNA expression were also evaluated. Morphologic, clinical, and follow-up data were reviewed. Twenty-five out of 87 non-AITL cases (28.75%) showed PD-1 immunostaining. CXCL13, BCL6, and CD10 expression was found in 24/25 (96%), 16/25 (64%), and 6/25 (24%) cases, respectively. All cases expressed at least 2 TFH cell markers. Moreover, 5 cases were positive for all 4 markers. Most cases (17/25, 68%) displayed some AITL-like features. Of the remainder, 1 was considered to be early AITL, 1 was diagnosed as ALCL-anaplastic lymphoma kinase-negative, and 4 of the other 6 PTCLs-U had morphology consistent with lymphoepithelioid (Lennert's) lymphoma. Three AITL-like cases showed IgH clonal rearrangement, 2 of which were associated with Epstein-Barr virus expression. Our series of patients did not differ significantly in their clinical presentation from most reported PTCL cases in the literature: 55% of them were alive and 35% were in complete remission after a median follow-up of 15 months after cyclophosphamide, dexorubicin, vincristine, and prednisone-based chemotherapy. TFH cell markers, especially PD-1, were expressed in a subset of PTCLs not classified as AITL, although most of them shared some morphologic features with AITL. This suggests that the spectrum of AITL may be wider than previously thought, possibly including cases of lymphoepithelioid (Lennert's) lymphoma. Additionally, the results suggest that a subgroup of PTCLs-U, distinct from AITL and including some cases denominated as ALCL, may also be derived from TFH cells, although they develop along a distinct pathogenic pathway. | 18,779,728 |
Compartment syndrome of the foot after calcaneal fractures. | A compartment syndrome is a condition in which high pressure within a closed fascial space causes reduced blood flow with nerve and muscle ischaemia. Untreated compartment syndrome leads to ischaemia with necrosis, contractures, myofibrosis and irreversible functional impairment in the involved part of the limb. Calcaneal fractures and other kinds of foot trauma may cause acute compartment syndrome of the foot. This condition may lead to foot deformities, including clawing of the toes, weakness of the foot muscles and, ultimately, a gait disorder. We studied 13 patients with unilateral calcaneal bone fractures. The healthy feet were examined as a control group. Data were derived from histories, physical examinations and measurements of intracompartmental pressure in three muscle compartments of the foot. Pressure in the foot with a calcaneal fracture was significantly higher than that on the healthy side, with pressures of 68.6 mmHg vs. 18.8 mmHg (p=0.0002) in the calcaneal (central) compartment, 49.0 mmHg vs. 14.4 mmHg (p=0.0003) in the lateral compartment, and 45.9 mmHg vs. 11.8 mmHg (p=0.0003) in the medial compartment. The pressures correlated with pain intensity rated by patients on a 10-point scale. Calcaneal fractures are accompanied by elevated intracompartmental pressure and symptoms of compartment syndrome. Acute compartment syndrome of the foot is very rarely diagnosed in Poland and only exceptionally treated by compartmental decompression. If left untreated, combined with deformities directly related to the fracture, it may lead to disability. | 18,779,771 |
Characterization of pancreatic ductal cells in human islet preparations. | Substantial amounts of nonendocrine cells are implanted as part of human islet grafts, and a possible influence of nonendocrine cells on clinical islet transplantation outcome has been postulated. There are currently no product release criteria specific for nonendocrine cells due to lack of available methods. The aims of this study were to develop a method for the evaluation of pancreatic ductal cells (PDCs) for clinical islet transplantation and to characterize them regarding phenotype, viability, and function. We assessed 161 human islet preparations using laser scanning cytometry (LSC/iCys) for phenotypic analysis of nonendocrine cells and flow cytometry (FACS) for PDC viability. PDC and beta-cells obtained from different density fractions during the islet cell purification were compared in terms of viability. Furthermore, we examined PDC ability to produce proinflammatory cytokines/chemokines, vascular endothelial growth factor (VEGF) and tissue factor (TF) relevant to islet graft outcome. Phenotypic analysis by LSC/iCys indicated that single staining for CK19 or CA19-9 was not enough for identifying PDCs, and that double staining for amylase and CK19 or CA19-9 allowed for quantitative evaluation of acinar cells and PDC content in human islet preparation. PDC showed a significantly higher viability than beta-cells (PDC vs beta-cell: 75.5+/-13.9 and 62.7+/-18.7%; P<0.0001). Although beta-cell viability was independent of its density, that of PDCs was higher as the density from which they were recovered increased. There was no correlation between PDCs and beta-cell viability (R(2)=0.0078). PDCs sorted from high-density fractions produced significantly higher amounts of proinflammatory mediators and VEGF, but not TF. We conclude that PDCs isolated from different fractions had different viability and functions. The precise characterization and assessment of these cells in addition to beta-cells in human islet cell products may be of assistance in understanding their contribution to islet engraftment and in developing strategies to enhance islet graft function. | 18,779,781 |
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