title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Rac1 mediates phorbol 12-myristate 13-acetate-induced migration of glioblastoma cells via paxillin. | Previously, we reported that phorbol 12-myristate 13-acetate (PMA)-activated protein kinase C (PKC) induced Rac1 activation in A172 glioblastoma cells. In this study, we investigated the mechanism of PMA-activated PKC-induced migration of glioblastoma cells by focusing on Rac1. PMA-induced formation of lamellipodia and focal complexes following migration were blocked by inhibiting Rac1 with small interfering RNA (siRNA), implicating Rac1 in PMA-induced glioblastoma cell migration. PMA-activated PKC induced phosphorylation of c-jun N-terminal kinase (JNK), one of the downstream effectors of Rac1. Immunohistochemical analysis showed that phosphorylated JNK was translocated to paxillin-containing focal complexes upon PMA stimulation and that Rac1 siRNA blocked these phenomena. These results suggest that phosphorylated JNK functions in cell migration and that JNK phosphorylation and translocation are mediated by Rac1. Furthermore, inhibition of Rac1 reduced phosphorylation of paxillin, a focal adhesion component and a downstream effector of JNK, at serine 178 (Ser178). Paxillin phosphorylation at this site has been shown to be involved in cell migration. Immunohistochemical analysis detected phosphorylation of paxillin (Ser178) in focal complexes upon PMA stimulation that was blocked by Rac1 siRNA. SP600125, a JNK inhibitor, also blocked PMA-induced phosphorylation of paxillin and aggregation of phosphorylated paxillin (Ser178) in focal complexes. In conclusion, paxillin is a critical downstream effector of Rac1 that may be involved in PMA-stimulated migration presumably by modulating the integrity of focal complex formation. | 18,813,807 |
Activation of Akt-mTOR-p70S6K pathway in angiogenesis in hepatocellular carcinoma. | Angiogenesis is an essential process for progression of hepatocellular carcinoma (HCC). The Akt-mTOR-p70S6K signal pathway has been recognized for its roles in regulating neoangiogenesis. The role of activation of the pathway in HCC progression is poorly understood. This study aimed to evaluate the immunohistochemical expression of the phosphorylated forms of the three key constituent proteins (Akt, mTOR and p70S6K) of the Akt-mTOR-p70S6K signal pathway in HCC and non-HCC tissue. Formalin-fixed paraffin-embedded tissue sections of 51 HCC, 9 hepatocellular adenoma (HCA), 48 cirrhotic nodules (CN) and 17 normal liver tissues (NLT) were immunostained for p-Akt, p-mTOR and p-p70S6K. The number of p-Akt and p-p70S6K-positive sinusoidal endothelial cells (SEC) and the intensity of immunostaining were significantly increased in HCC compared with HA, CN and NLT (p<0.01). p-mTOR in SEC tended to have an increased expression in SEC in HCC versus non-HCC tissue (p>0.05). There was a significant correlation between a high p-Akt and p-p70S6K expression, and a venous and capsular invasion of HCC. Our results suggest that activation of the Akt-mTOR-p70S6K pathway plays a significant role in HCC progression by promoting neoangiogenesis. Molecular strategies aimed at inhibiting this signal pathway may be of therapeutic use for the treatment of HCC. | 18,813,808 |
Yanhusuo extract inhibits metastasis of breast cancer cells by modulating mitogen-activated protein kinase signaling pathways. | Yanhusuo (Corydalis yanhusuo W.T. Wang) is a well-known traditional Chinese medicine (TCM). In this study, we attempted to characterize in detail the signaling cascades that produce its anti-metastatic effect on the human breast cancer cell line, MDA-MB-231. We found that the yanhusuo extract inhibited the migration and invasion of MDA-MB-231 cells in vitro. In addition, the yanhusuo extract inhibited the mRNA expression and activity of metalloproteinase-9 (MMP-9). The anti-cancer metastasis effect of yanhusuo involved the activation of p38 and inhibition of ERK1/2 and SAPK/JNK mitogen-activated protein kinase (MAPK) signaling. Our experiments identified the biological activity of yanhusuo against cancer metastasis in vitro and provide a rationale for its further investigation. | 18,813,823 |
Stat3 as a molecular target in RNA interference-based treatment of oral squamous cell carcinoma. | Constitutive activation of signal transducer and activator of transcription 3 (Stat3) has been observed in many human malignancies. Using the sequence-specific RNA interference (RNAi) method to switch off Stat3 expression, it may be possible to arrest cancer growth. In this study, we aimed to identify the most effective sequence of a synthetic small interfering RNA (siRNA) specific for Stat3 (Stat3-siRNA) and the effect of Stat3 suppression on the growth of oral squamous cell carcinoma cells. Ten designed siRNAs with known sequences were screened for the best RNAi effect at the working concentrations of 1 and 10 nM. The range of reduction of Stat3 expression varied from 21 to 67% for 10 nM siRNAs, and from 13 to 73% for 1 nM siRNAs. Three out of the 10 screened siRNAs reduced Stat3 expression to lower levels compared with the GFP-siRNA control. The interferon response of some siRNAs was observed at a concentration of 10 nM. However, at 1 nM, the mRNA levels of interferon response genes (OAS1, OAS2, MX1 and ISFG3gamma) remained unchanged. The growth of GFP-SAS, HSC-3, HSC-4 and KB cells was strongly inhibited by the use of three effective Stat3-siRNAs in comparison with other Stat3-siRNAs and GFP-siRNA. Moreover, the mRNA levels of genes for which transcription is activated by Stat3 were markedly suppressed. These results suggest that targeting Stat3 using siRNA may constitute a useful approach for the treatment of oral squamous cell carcinoma. | 18,813,829 |
Positive regulation of migration and invasion by vasodilator-stimulated phosphoprotein via Rac1 pathway in human breast cancer cells. | This study aimed to investigate the role of the cytoskeleton-associated protein vasodilator-stimulated phosphoprotein (VASP) on the migration and invasion of human breast cancer cells and its relationship to Rac1 which is a member of the Rho family and has been found to be implicated in tumorigenesis, invasion and metastasis. We detected the mRNA and protein expression levels of VASP and Rac1 of the non-invasive breast cancer cell line MCF-7 as well as the invasive cell line MDA-MB-231 by RT-PCR and Western blotting. GST pull-down assay was used to examine the activity of Rac1. Accordingly, the cell invasive migration ability was analyzed in a wound-healing assay (2D) and transwell assays (3D migration and invasion). We then used VASP-siRNA to inhibit the expression of VASP in breast cancer cells in order to study the relationship between the VASP expression level and the invasive migration ability of breast cancer cells. Rac1-siRNA was used to decrease the expression of Rac1, and observe its effect on the VASP expression level together with the migration and invasion ability of MCF-7 and MDA-MB-231 cells. Our results revealed that the invasive breast cancer cell line MDA-MB-231 showed a higher Rac1 activity and VASP expression level compared with the non-invasive MCF-7. Inhibition of Rac1 or VASP by siRNA, respectively, decreased the migration and invasion ability of breast cancer cells and the transfection of Rac1 siRNA-mediated reduction of VASP expression at mRNA and protein levels. Collectively, our data showed that the higher expression level of VASP contributed to a higher invasive migration capacity of human breast cancer cells which was controlled by the Rac1 pathway. | 18,813,837 |
Urokinase-type plasminogen activator receptor is associated with macrophages and plaque rupture in symptomatic carotid atherosclerosis. | There is a strong correlation between macrophage infiltration and plaque instability in recently symptomatic carotid atherosclerotic plaques, and it is hypothesised that mechanisms related to macrophages may be involved in plaque vulnerability and rupture. We previously found high expression of urokinase-type plasminogen activator receptor (UPAR) in human macrophages. The aim of this study was to investigate whether UPAR co-localises with macrophages in symptomatic carotid plaques, and whether UPAR expression is associated with plaque rupture. Real-time RT-PCR assays showed that UPAR expression levels were high in monocyte-derived macrophages and in carotid endarterectomies compared with a tissue panel. Serial transverse sections were prepared from carotid endarterectomies from 12 symptomatic patients, and analyzed with immunohistochemical staining for UPAR and for CD68-positive macrophages, and with histopathological assessment. UPAR co-localised with CD68-positive macrophages, with a high correlation (r=0.90, p<0.001) between immunostained areas in 12 carotid endarterectomies from symptomatic patients. High degrees of UPAR and CD68 staining were found in sections around the bifurcation level where rupture was most common, while low degrees of staining were found in sections of the common carotid artery end of the endarterectomy (p<0.05). Higher degrees of UPAR staining were observed in ruptured plaque sections compared with non-ruptured sections. In conclusion, UPAR was highly expressed in monocyte-derived macrophages and in symptomatic carotid plaques, UPAR co-localised with macrophages in carotid symptomatic plaques and UPAR was predominantly found in ruptured plaque segments. These findings support the hypothesis that UPAR is related to plaque rupture in symptomatic atherosclerotic lesions. | 18,813,852 |
Evaluation of novel cyclic analogues of apelin. | Apelin regulates various cell signaling processes through interaction with its specific cell-surface receptor, APJ, which is a member of a seven transmembrane G protein-coupled receptor superfamily. To develop a novel apelin analogue, we synthesized cyclic analogues of minimal apelin fragment RPRLSHKGPMPF (apelin-12), and evaluated their bioactivities in a recombinant human APJ-expressed cell line. Three cyclic analogues were synthesized: cyclo apelin-12 (C1) in combination with amino-terminal to carboxy-terminal, cyclourea apelin-12 (C3) in combination with amino-terminal and amino acid side chain at positions 7, and cyclic apelin-12 (C4) in combination with amino acid side chain at positions 7 to carboxy-terminal. All cyclic analogues exhibited dose-dependent inhibitory effects against forskolin-induced cyclic adenosine monophosphate (cAMP) accumulation, and the maximal effects were almost abolished by pertussis toxin (PTx) treatment. Moreover, they could modulate the intracellular signaling pathways composed of Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) serine/threonine protein kinases in PTx-sensitive manner. This is the first approach to apply cyclization on apelin, and these results provide the basis for the development of drug-like apelin analogues. | 18,813,863 |
Adaptive immunity to the obligate intracellular pathogen Coxiella burnetii. | Coxiella burnetii is an obligate intracellular bacterial pathogen that causes the zoonosis Q fever. While an effective whole-cell vaccine (WCV) against Q fever exists, the vaccine has limitations in being highly reactogenic in sensitized individuals. Thus, a safe and effective vaccine based on recombinant protein antigen (Ag) is desirable. To achieve this goal, a better understanding of the host response to primary infection and the precise mechanisms involved in protective immunity to C. burnetii are needed. This review summarizes our current understanding of adaptive immunity to C. burnetii with a focus on recent developments in the field. | 18,813,881 |
Anticoagulant and/or antiplatelet treatment in patients with atrial fibrillation after percutaneous coronary intervention. A single-center experience. | Atrial fibrillation (AF) is the most common cardiac arrhythmia sustained and frequently occurs in patients with coronary heart disease. Thus, a large number of patients requiring percutaneous coronary intervention (PCI) also suffer from AF. An anticoagulant regimen has not been standardized for patients with AF after coronary stent implantation. The authors investigated data from 159 patients with AF who underwent PCI in their department. Baseline variables and incidence of a combined endpoint (stroke, myocardial infarction, cardiovascular death, severe bleeding) were compared in patients receiving clopidogrel and acetylsalicylic acid (ASA; group 1) versus patients receiving the combination of clopidogrel and ASA with low-molecular-weight heparin (LMWH; group 2) versus patients receiving the combination of clopidogrel and ASA with oral anticoagulation (OAC; group 3) at discharge. Patients discharged with triple therapy including OAC seemed to be at higher risk: patients in group 3 had decreased left ventricular ejection fraction and increased inflammatory state as measured by plasma fibrinogen and C-reactive protein. Moreover, previous OAC treatment and strokes were found more often in this subgroup of patients. In a median follow-up of 1.4 years, two severe bleeding events (both in group 1), four myocardial infarctions (all in group 1), 13 strokes (nine in group 1, four in group 2), and nine cardiovascular deaths (three in group 1, five in group 2, one in group 3) occurred. In this analysis, no treatment regimen seemed to be clearly superior. It underlines the importance of prospective, randomized trials to investigate the optimal antithrombotic/antiplatelet treatment for patients with AF after PCI. | 18,813,885 |
Physiotherapy does not prevent, or hasten recovery from, ventilator-associated pneumonia in patients with acquired brain injury. | To investigate the effect of respiratory physiotherapy on the prevention and treatment of ventilator-associated pneumonia (VAP) for adults in an intensive care unit (ICU) with an acquired brain injury (ABI). Two-part, prospective, randomised controlled trial. A total of 144 subjects with ABI admitted with a Glasgow Coma Scale </=9, requiring intracranial pressure monitoring, and invasive mechanical ventilation (MV) for >24 h; 33 subjects were subsequently diagnosed with VAP. Respiratory physiotherapy comprised six treatments (positioning, manual hyperinflation and suctioning) in each 24-h period whilst on MV. The Control Group received standard medical/nursing care but no respiratory physiotherapy. There were no significant differences between groups for incidence of VAP, duration of MV, length of ICU stay or clinical variables such as requirement for re-ventilation. In adults with ABI, regular respiratory physiotherapy in addition to routine medical/nursing care does not appear to prevent VAP, reduce length of MV or ICU stay. Due to small numbers, it is not possible to draw any conclusions as to whether or not respiratory physiotherapy hastens recovery from VAP. | 18,813,910 |
Endoscopic third ventriculostomy: the best option in the treatment of persistent hydrocephalus after posterior cranial fossa tumour removal? | Ten to 40% of children operated on for a posterior fossa tumour require a further surgical procedure for the management of a persisting active ventricular dilation. The management of this kind of hydrocephalus is still controversial. To prospectively evaluate the effectiveness of post-operative endoscopic third ventriculostomy (ETV) in the management of persistent active hydrocephalus in a series of children operated on for a posterior cranial fossa tumour. The management protocol consisted of: (1) placement of a peri-operative antibiotic impregnated external ventricular catheter (Bactiseal) and tumour removal, (2) post-operative intracranial pressure (ICP) monitoring through the external ventricular drainage, (3) ETV in case of persistent ventricular dilation and persistently abnormal high ICP values and (4) ventriculoperitoneal shunt implantation in case of ETV failure. Thirty on a total of 104 children (28.8%) operated on between January 2001 and February 2007 at our institution needed a further surgical treatment for the persistence of the hydrocephalus after the removal of their posterior cranial fossa tumour. They were sub-divided in two groups according to the early (group 1--21 patients) or later (group 2--nine patients) definition of the persistence of an active ventricular dilation based on clinical, radiological and ICP monitoring data. ETV was successful in 90.0% of the patients in the present series (27/30 patients), without statistically significant differences among the two groups considered. Post-operative ETV should be considered the best option to treat persistent hydrocephalus after the removal of posterior fossa tumours. | 18,813,936 |
Identification of SLC26A4 gene mutations in Iranian families with hereditary hearing impairment. | Mutations in the SLC26A4 gene at the DFNB4 locus are responsible for Pendred syndrome and non-syndromic hereditary hearing loss (DFNB4). This study included 80 nuclear families with two or more siblings segregating presumed autosomal recessive hearing loss. All deaf persons tested negative for mutations in GJB2 at the DFNB1 locus and were, therefore, screened for autozygosity by descent (ABD) using short tandem repeat polymorphisms (STRPs) that flanked SLC26A4. In 12 families, homozygosity for STRPs suggested possible ABD in this genomic region. Affected individuals in five families had a positive perchlorate discharge test. Sequence analysis of SLC26A4 identified ten mutations in eight families (T420I, 1197delT, G334V, R409H, T721M, R79X, S448L, L597S, 965insA and L445W), of which, four are novel (T420I, G334V, 965insA and R79X). These results imply that Pendred syndrome is the most prevalent form of syndromic hereditary hearing loss in Iran. | 18,813,951 |
New data on ectomycorrhizae and soils of the Chinese truffles Tuber pseudoexcavatum and Tuber indicum, and their impact on truffle cultivation. | Chinese truffles serve as a good complement to the market for Tuber melanosporum (Périgord black truffle). However, Chinese truffles could be introduced accidentally or fraudulently into the plantations of Mediterranean truffles, and they could have a negative effect on truffle production and natural ecosystems. The study of Tuber species from China which are commercialized in Europe began 14 years ago. Tuber pseudoexcavatum was proposed as a new species, and this has been validated by some authors based on molecular and phylogenetic studies. We synthesize their ectomycorrhizae using samples from the type collection, and we compare T. pseudoexcavatum and Tuber indicum ectomycorrhizae. The ectomycorrhizae of these species have a morphology which is related to the ectomycorrhizae of T. melanosporum. We provide useful information for the rapid screening of the above-mentioned Chinese truffles ectomycorrhizae, for the quality control of commercial plants mycorrhized with Tuber. Moreover, we analyze the soil tolerance and the host plant affinity of T. pseudoexcavatum and T. indicum, in order to assess the capacity of both Chinese truffles to penetrate T. melanosporum plantations and habitats. | 18,813,959 |
Expert benchmark for the GI Mentor II. | There is increasing interest in the use of virtual-reality simulators in general surgery residency training. Many simulators lack a benchmark against which trainees can measure competence and skill. Surgeons who had performed over 1,000 colonoscopies were evaluated on module 1, case 5 of the GI Mentor I or II virtual-reality endoscopy simulator (Simbionix, Cleveland). Participants were given 5 min to familiarize themselves with the simulator, and then performed the study case with standardized instructions. Metrics were recorded by using the previously calibrated simulator. Twenty-three surgeons (21 male, 2 female) participated. Mean height was 69.6 +/- 2.6 inches, mean age 51 +/- 9 years, median surgical glove size 7.5, and surgeons had 18.8 +/- 10.1 years of practice, and did 8 +/- 6 colonoscopies weekly. Ten participants had advanced training in endoscopy, laparoscopy or colorectal surgery; eight had used the simulator before, of whom six had used it once. Mean time to complete the study case was 13.6 +/- 5.3 min and time to reach the cecum was 6.5 +/- 4.3 min. Participants examined 92.3 +/- 3.6% of the simulated colonic mucosa with a clear view of the lumen 89.5 +/- 4.2% of the time. Total time the colon was looped was 22 +/- 35 s (range 0-133 s). The overall efficiency of screening was 70.33 +/- 23.45% (range 20-94%). Participants tended to mistake normal simulated colonic structures as pathology. Performance on a virtual-reality endoscopic simulator has a wide amount of variability even among a group of experienced endoscopists. Expert benchmark tests should be performed on simulators that will be used for resident assessment prior to any attempts at certification of competence. | 18,813,977 |
What is going on in augmented reality simulation in laparoscopic surgery? | To prevent unnecessary errors and adverse results of laparoscopic surgery, proper training is of paramount importance. A safe way to train surgeons for laparoscopic skills is simulation. For this purpose traditional box trainers are often used, however they lack objective assessment of performance. Virtual reality laparoscopic simulators assess performance, but lack realistic haptic feedback. Augmented reality (AR) combines a virtual reality (VR) setting with real physical materials, instruments, and feedback. This article presents the current developments in augmented reality laparoscopic simulation. Pubmed searches were performed to identify articles regarding surgical simulation and augmented reality. Identified companies manufacturing an AR laparoscopic simulator received the same questionnaire referring to the features of the simulator. Seven simulators that fitted the definition of augmented reality were identified during the literature search. Five of the approached manufacturers returned a completed questionnaire, of which one simulator appeared to be VR and was therefore not applicable for this review. Several augmented reality simulators have been developed over the past few years and they are improving rapidly. We recommend the development of AR laparoscopic simulators for component tasks of procedural training. AR simulators should be implemented in current laparoscopic training curricula, in particular for laparoscopic suturing training. | 18,813,987 |
Sexual function after sacrospinous fixation for vaginal vault prolapse: bad or mad? | The main indication for sacrospinous ligament suspension is to correct either total procidentia, a posthysterectomy vaginal vault prolapse with an associated weak cardinal uterosacral ligament complex, or a posthysterectomy enterocele. This study aimed to evaluate sexual function and anatomic outcome for patients after sacrospinous ligament suspension. For this study, 52 patients who had undergone sacrospinous ligament fixation during the preceding 5 years were asked to complete the Female Sexual Function Index (FSFI) questionnaire. The patients were vaginally examined using the ICS POP score, and the results were compared with their preoperative status. For statistical analysis, GraphPad for Windows, version 4.0, was used. The 52 patients were examined during a follow-up period of 38 months. No major intraoperative complications were noted. Recurrence of symptomatic apical descent was noted in 6% of the patients and de novo prolapse in 13.5%. Only one patient was symptomatic. Three patients experienced de novo dyspareunia, which resolved in two cases after stitch removal. Sexual function was good, rating higher than three points for each of the domains including satisfaction, lubrication, desire, orgasm, and pain. Sacrospinous ligament fixation still is a valuable option for the treatment of vaginal vault prolapse. Sexual function is satisfactory, with few cases of de novo dyspareunia. | 18,814,009 |
Proteomic analysis of mammary tissues from healthy cows and clinical mastitic cows for identification of disease-related proteins. | To investigate the disease-related proteins and understand molecular mechanism of mastitis at the protein level, this project presents the protein changes in the mammary gland between healthy cows and clinical mastitic cows using two-dimensional gel electrophoresis (2-DE), after stained with colloidal Coomassie Bright Blue, six spots of differentially expressed protein were detected by PDQuest software and subjected to ion trap mass spectrometer equipped with a HPLC system, and five proteins were identified. Hemoglobin beta, kappa-casein and tryptophanyl-tRNA-synthetase (TrpRS) in healthy dairy cows, while hemoglobin beta, cytochrome C oxidase and annexin V in clinical mastitic cows were identified, they were involved in binding, transport and catalytic activity. The results may provide valuable information for the investigating of the host mammary immune system response to defense against pathogens at the protein level and potential protein targets for treatment. | 18,814,050 |
[Winter sports and shoulder arthroplasty]. | Nowadays, a general negative evaluation of sportive activity regarding different kinds of sport following arthroplasty is at present no more scientifically supported. However, at present no valid guidelines regarding sportive activity of patients after implantation of shoulder joint arthroplasty exist. The question regarding the ability of performing winter sports activities of patients treated with shoulder joint endoprothesis has not been answered so far. Therefore the aim of the presented work was to identify winter sports-specific risks for patients treated with shoulder joint endoprothesis as well as to critically discuss the actual literature in refer to winter sport activities. Criteria for the education of patients with shoulder joint endoprothesis as well as consultation regarding winter sport activities will be provided for the orthopaedic surgeon. | 18,814,057 |
[Damping inserts have no load reducing effect in the fatigued state]. | Overload injuries to the lower limbs may be attributed to repetitive, non-physiological load stimuli. However, these impact loads acting on the musculoskeletal can be reduced by wearing damping inserts. To date, however, there is only little evidence as to whether this positive effect can be assigned to the damping insert and, furthermore, whether this effect is detectable in states of muscle fatigue. Therefore, the influence of muscle fatigue in combination with the wearing of damping inserts was investigated in 13 subjects. The parameters examined in this study were ground reaction forces during walking and the muscular activation profile of the lower limb in the phase of initial ground contact. The results showed that neither in comparisons with and without damping inserts nor in states of muscular fatigue could significant differences were found in the ground reaction forces. Wereas, no significant differences could be detected in the investigated muscles, with and without damping inserts, preactivation in the peroneal and biceps femoris muscles were significantly earlier, in states of muscular fatigue with damping inserts, while no changes could be found in the anterior tibial, soleus, vastus lateralis and gastrocnemius muscles. The present results demonstrate that wearing damping inserts does not lead to a positive effect with regard to a reduction of the ground reaction forces. The earlier preactivation in the case of muscle fatigue with a damping insert is indicative of an increased energy expenditure which may be possibly associated with increased knee and ankle joint control. The high satisfaction concerning the comfort of wearing such inserts revealed by a questionnaire did not correlate with a reduction in loading condition. On the basis of the present results we cannot recommend the wearing of damping soft sole inserts in the context of a reduction in load condition. | 18,814,060 |
Hepatic vascular malformations in hereditary hemorrhagic telangiectasia. | Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that can involve the liver diffusely in the form of vascular malformations ranging from small telangiectases to discrete arteriovenous malformations. Anatomically, three different patterns of abnormal vascular communications can occur in liver: portal vein to hepatic vein (portovenous), hepatic artery to hepatic vein (arteriovenous) and hepatic artery to portal vein (arterioportal), with the most common being arteriovenous. Only 5 to 8% of patients with these vascular malformations are symptomatic. When symptomatic, patients present with high-output cardiac failure, biliary ischemia (which, when severe, can progress to biliary and hepatic necrosis and lead to acute liver failure), or portal hypertension. Other less common presentations include portosystemic encephalopathy and abdominal angina. Diagnosis is confirmed by Doppler ultrasonography or multidetector computed tomography. The hallmark findings are intrahepatic hypervascularization and an enlarged common hepatic artery. Focal nodular hyperplasia and nodular regenerative hyperplasia are common findings. Symptomatic patients are treated with intensive medical treatment aimed at the predominant clinical presentation. Patients who fail aggressive medical therapy and those with acute biliary/hepatic necrosis should be considered for liver transplantation. | 18,814,078 |
[Combination therapy in patients with pulmonary arterial hypertension]. | Despite recent remarkable efforts in the medical treatment options of patients with pulmonary arterial hypertension (PAH) a considerable number of patients need escalations to improve disease related symptoms and pulmonary hemodynamics. Most of the pulmonary vascular vasodilators have been approved in its potency as an initial and sole medical option. However, there is increasing scientific evidence on the reliability, safety and effectiveness of possible combinations. This paper reviews the current scientific literature about medical escalations and combination therapy in patients with PAH. | 18,814,093 |
[Decompensated pulmonary hypertension]. | Right ventricular failure may result from an newly developed disease (e.g. as a consequence of acute respiratory distress syndrome [ARDS] or of severe pulmonary embolism) or of already present pulmonary hypertension (PHT). There is as yet no generally recognized definition of acute or chronic right ventricular failure. The particular clinical picture and the associated hemodynamics determine this condition. Right ventricular failure in the course of PHT represents a great challenge in clinical and intensive care practice. Once the vicious circle of right heart failure is reached an optimal balance has to be found between preload and afterload. In addition to optimizing blood volume, positive inotropic drugs (e.g. dobutamine) are available to maintain systemic blood pressure. Furthermore an increase in right ventricular contractility by inodilators is aimed at. The central goal in the treatment of right heart failure as part of PHT is to lower pulmonary vascular resistance and thus decrease right ventricular afterload. However, it is very difficult to break the vicious circle involved in the acute right heart syndrome, it must be the primary aim of treatment to recognize as early as possible any worsening of PHT and prevent acute right heart failure. Lung transplantation or surgical atrioseptostomy may represent possible ultimate therapeutic options for patients with PHT. | 18,814,101 |
[Assessment of the solid-liquid behavior of the liver for the diagnosis of diffuse disease using magnetic resonance elastography]. | Recent magnetic resonance elastography (MRE) studies have reported the potential of this noninvasive method for diagnosing hepatic fibrosis based on the elastic properties of liver tissue. However, in many cases biological tissue responds to mechanical vibrations as a combined solid-liquid body causing MRE-derived elastic parameters to become functions of the applied vibration frequency. Therefore a multi-frequency MRE study of liver was performed and the potential of the method for separating healthy from fibrotic liver was investigated. The aim of this study was the increase of the accuracy of liver elastography by analyzing multi-frequency MRE examinations using the springpot model. 18 healthy volunteers and 10 patients were examined by multi-frequency MRE of the liver in a frequency range between 25 Hz and 62.5 Hz. The liver was mechanically excited with four harmonic vibrations simultaneously. The measured dispersion of the complex modulus was analyzed using the springpot model which accounts for both elastic and viscous properties of a material with 2 independent parameters. The mechanical stimulation and the motion encoding according to the multi-frequency approach was implemented successfully. Significant differences (p < 0.05) were found in the hepatic viscoelasticities of normal livers. The separation of healthy volunteers and patients was achieved with a sensitivity and specificity of 80 and 100 %, respectively. Using the springpot model, multi-frequency MRE is sensitive to interindividual differences in the hepatic viscoelastic properties of healthy volunteers. The obtained accuracy of the technique in separating healthy from fibrotic livers opens the possibility of applying multi-frequency MRE as a noninvasive method for diagnosing liver fibrosis in the future. | 18,814,103 |
[Neurogenic communication disorders: how effective are relaxation therapy and acupuncture?]. | Not only neurologists but also ENT-physicians and phoniatricians have to prescribe speech and language therapy for patients with communication disorders. Complementary and alternative medicine (CAM) has gained increasing popularity among patients. Many studies have investigated these procedures and positive effects on certain physical e. g., chronic pain and anxiety disorders could be validated. Unfortunately only few empirical investigations have targeted the use of CAM to treat neurogenic disorders of communication or cognition. In this review we provide an overview over general therapeutical principals of two widely used approaches, relaxation therapy and acupuncture. Then we survey the literature and summarize existent research literature regarding the effects of the treatment of neurogenic disorders including dementia. | 18,814,104 |
Iliocaval arteriovenous fistula following lumbar disc surgery: endovascular treatment with a Stent-graft. | Arteriovenous (AV) fistulae, pseudoaneurysms, and lacerations may occur during disc surgery. AV fistula after lumbar disc surgery is rare. Early diagnosis and treatment of vascular complications associated with disc surgery is essential due to their high mortality and morbidity rates. We report a case report who was presented with fistulous shunt between right common iliac artery and inferior vena cava fifteen days after operation for herniated discs at L4-L5 and L5-S1 levels. Treatment was transcatheter covered stent placement at the fistulous site of right common iliac artery using a self expandable stent-graft. We suggest use of minimally invasive interventional techniques in the management of suitable vascular injuries following lumbar disc surgery. | 18,814,112 |
A large choroid plexus papilloma removed by the cerebellomedullary fissure approach. Case report and review of the literature. | We report a case of large choroid plexus papilloma of the fourth ventricle in a 23-year-old woman. She presented with severe headache, dysphagia, and gait disturbances. Horizontal nystagmus, ataxic gait and quadriparesis were detected on initial examination. Imaging studies showed a large mass in the left side of brain stem and a marked hydrocephalus. The tumour was removed by microsurgical dissection of the cerebellomedullary fissure. We have discussed the effectiveness of this approach for removal of bulky tumors of the fourth ventricle and reviewed the literature about its benefits and potential hazards. | 18,814,123 |
Multiplexed lipid dip-pen nanolithography on subcellular scales for the templating of functional proteins and cell culture. | Molecular patterning processes taking place in biological systems are challenging to study in vivo because of their dynamic behavior, subcellular size, and high degree of complexity. In vitro patterning of biomolecules using nanolithography allows simplification of the processes and detailed study of the dynamic interactions. Parallel dip-pen nanolithography (DPN) is uniquely capable of integrating functional biomolecules on subcellular length scales due to its constructive nature, high resolution, and high throughput. Phospholipids are particularly well suited as inks for DPN since a variety of different functional lipids can be readily patterned in parallel. Here DPN is used to spatially pattern multicomponent micro- and nanostructured supported lipid membranes and multilayers that are fluid and contain various amounts of biotin and/or nitrilotriacetic acid functional groups. The patterns are characterized by fluorescence microscopy and photoemission electron microscopy. Selective adsorption of functionalized or recombinant proteins based on streptavidin or histidine-tag coupling enables the semisynthetic fabrication of model peripheral membrane bound proteins. The biomimetic membrane patterns formed in this way are then used as substrates for cell culture, as demonstrated by the selective adhesion and activation of T-cells. | 18,814,174 |
Iron deficiency anemia and affective response in rhesus monkey infants. | Infant iron deficiency anemia (IDA) occurs spontaneously in monkey populations as it does in humans, providing a model for understanding effects on brain and behavior. A set of 34 monkey infants identified as IDA (hemoglobin <11 g/dl) over a 5-year period at the California National Primate Research Center (CNPRC) was compared to a set of 57 controls (hemoglobin >12 g/dl) matched for age and caging location. The infants had participated in a Biobehavioral Assessment conducted at 3-4 months of age at CNPRC that included measures of behavioral and adrenocortical response to a novel environment. IDA males differed from control males in two factors ("activity," "emotionality") derived from observational data taken on the first and second day of the exposure to the novel environment. In the male infants, IDA was associated with less restriction of activity in the novel environment on both days and less emotionality on the second day (p < .05). IDA males also displayed less response to approach by a human (human intruder test) than did control males. IDA females did not differ from controls. Adrenocortical response was not significantly affected. These findings may be relevant to functional deficits in human infants with IDA that influence later behavior. | 18,814,183 |
Long-term sustained benefits of clozapine treatment in refractory early onset schizophrenia: a retrospective study in Korean children and adolescents. | Treatment resistance in early onset schizophrenia (EOS) is one of the most challenging problems in child and adolescent psychiatry. We retrospectively examined the therapeutic dosage, clinical response, and side effect profiles of long-term clozapine treatment in Korean children and adolescents with refractory EOS or very early onset schizophrenia (VEOS). 26 refractory patients treated with clozapine for more than 1 year were analyzed. Efficacy was determined by comparing hospitalization rate and duration, before and after clozapine treatment. Tolerability was assessed through review of documented adverse events. A significant reduction in hospital days per year was observed in 25 (96.2%) patients after clozapine treatment compared to before clozapine. Long-term benefit of the treatment was supported by a further reduction of the hospitalization rate in 14 patients treated with clozapine for more than 3 years. Neutropenia developed in 26.9% patients at 1 year and there was no agranulocytosis. Overall, eight male patients (8/12, 66.7%) and one female patient (1/14, 7%) developed neutropenia and out of the nine patients, seven patients were maintained and two patients were successfully rechallenged on clozapine. These findings suggest that long-term clozapine treatment may effectively reduce the amount of time Asian patients with refractory EOS or VEOS spend in the hospital. However careful monitoring of adverse events is required. | 18,814,190 |
Separation of flavins and nicotinamide cofactors in Chinese hamster ovary cells by capillary electrophoresis. | Simultaneous extraction, separation and quantitation of reduced nicotinamide adenine dinucleotide (NADH), reduced nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) in Chinese Hamster Ovary (CHO) cells were investigated. The separation of flavins and nicotinamide cofactors was performed by capillary electrophoresis with laser-induced fluorescence detection at the excitation wavelength of 325 nm. The separation protocol was established by investigating the excitation wavelength, high voltage and effects of buffer nature, pH and concentration. All endogenous fluorophores riboflavin, FAD, FMN, NADH and NADPH show wide linear range of quantitation. The limits of detection for the five compounds ranged from 4.5 to 23 nM. Extraction conditions were optimized for high-efficiency recovery of all endogenous fluorophores from CHO cells. To account for the complex matrix of cell extracts, a standard addition method was used to quantify FAD, FMN, NADH and NADPH in CHO cells. The quantitative results should be useful to reveal the metabolic status of cells. The protocols for extraction, separation and quantitation are readily adaptable to normal and cancer cell lines for the analysis of endogenous fluorophores. | 18,814,195 |
Optimizing high-performance liquid chromatography method for quantification of glucosamine using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate derivatization in rat plasma: application to a pharmacokinetic study. | A sensitive and reliable HPLC method with fluorescence detection based on the precolumn derivatization of glucosamine with 6-aminoquinolyl-N-hydroxylsuccinimidyl carbamate (AQC) was established for the quantitative determination of glucosamine in rat plasma. The plasma protein was precipitated by acetonitrile, followed by vortex mixing and centrifugation. The supernatant was divided into the organic layer and aqueous layer by adding sodium chloride, and then the aqueous layer was derivatized with AQC in 0.2 M borate buffer of pH 8.8 before the HPLC analysis. An amino acid analysis column (3.9 x 150 mm, 4 microm) was applied, with 140 mM sodium acetate buffer (pH = 5.25) and acetonitrile as mobile phase at a flow rate of 1 mL/min. A linear correlation coefficient of 0.9987 was calculated within the range of 0.1-30 microg/mL of the standard curve for glucosamine. The limit of detection was 30 ng/mL. The intra- and inter-day precisions (as RSD) were less than 7.38 and 12.72%, respectively. The intra- and inter-day accuracy ranged from 91.8 to 110.0%. Extraction recoveries of glucosamine in plasma were more than 90%. The validated method was successfully applied for the quantitative determination of glucosamine in rat plasma and evaluation for pharmacokinetic study of glucosamine. It was also possible to be applied for the quantitative determination of other compounds containing amino group in biological samples. | 18,814,196 |
Techniques for chorionic villus sampling and amniocentesis: a survey of practice in specialist UK centres. | Guidelines exist for amniocentesis and chorionic villous sampling (CVS) practice, but there is no consensus regarding individual techniques. Our survey sought to review current practice within specialist centres in the United Kingdom. RCOG sub-specialist training centres were invited to complete a postal questionnaire, seeking their consultants' primary choices for amniocentesis and CVS techniques. Information sought included needle choice, local anaesthetic (LA), suction methods, quantity of samples obtained; and with regard to CVS, preferred approach [transcervical (TC) or transabdominal (TA)]. Response rate was 96% providing information on 111 consultants (111 amniocentesis/90 CVS). During amniocentesis, 86% use 22G needles and 70% are helped by an assistant who aspirates a set liquor volume (69%). For CVS, 98% use a TA approach, 89% use LA, and 29% an 18G single needle with 38% preferring a 17/19G double needle but no clear consensus regarding the use of assistants. There is some agreement among specialists in the United Kingdom regarding techniques for invasive prenatal diagnosis. For amniocentesis, most operators use 22G needles, with an assistant to aspirate a set volume of fluid regardless of gestation. For CVS, there is considerable variation in needle choice, although most operators use a TA approach with LA. | 18,814,215 |
ROCKs are expressed in brain tumors and are required for glioma-cell migration on myelinated axons. | The interactions between migrating glioma cells and myelinated fiber tracts are poorly understood. We identified that C6 glioma cells can migrate along myelinated chicken retinal axons in a novel coculture, thereby expressing small GTPases of the Rho family and serine/threonine Rho-associated kinases (ROCKs). We found that the ROCK1 isoform is also highly expressed in native human high-grade gliomas. Glioma cells migrated faster in vitro along myelinated axons than on laminin-1, with the former but not the latter being specifically and reversibly blocked by the ROCK inhibitor Y27632. These data suggest that the mechanisms underlying the migration of glioma cells on myelinated axons differ from those underlying the migration on extracellular matrix molecules such as laminin-1. | 18,814,230 |
mRNAs of tyrosine hydroxylase and dopa decarboxylase but not of GD2 synthase are specific for neuroblastoma minimal disease and predicts outcome for children with high-risk disease when measured at diagnosis. | Several transcripts have been claimed to be clinically valuable for detecting minimal disease in neuroblastoma, but they have not been prospectively compared in a standardized manner. Tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and GD2 synthase (GD2S) mRNAs were analyzed in 554 blood (PB) and bone marrow (BM) samples from 58 children with neuroblastoma. Samples from 44 children with other diseases served as controls. High transcript concentrations of TH, GD2S or DDC in PB or BM at diagnosis were associated with poor prognosis. TH in BM above median indicated worse outcome for a homogenous cohort with high-risk neuroblastoma (survival probability 91% for TH below median versus 33% for TH above median, p = 0.009). The number of children with localized neuroblastoma with increased results in PB did not differ between the three transcripts. In these children, all without morphologically detectable neuroblastoma in BM, the number of patients with elevated GD2S in BM at diagnosis was significantly higher than for the other transcripts (10/16 elevated, p = 0.012). GD2S was elevated in PB from 10/28 controls without neuroblastoma compared to 1/28 for TH and DDC (p < 0.001). In BM from these children GD2S was significantly elevated. We conclude that high expression of TH and DDC both in PB and BM corresponds to metastatic neuroblastoma at diagnosis, residual disease, and poor outcome. Children with high-risk neuroblastoma and low levels of TH in BM at diagnosis may be cured by current therapy. GD2S is less specific than TH and DDC mRNA for neuroblastoma detection in PB and BM. | 18,814,238 |
Intrafamilial transmission of hepatitis C virus: infection of the father predicts the risk of perinatal transmission. | The aims of the present study were to evaluate in a cohort of mothers infected with hepatitis C virus (HCV) the prevalence of HCV infection of their sexual partners, the influence of infection of the partners on perinatal transmission, and whether this influence is mediated by other well known risk factors for perinatal transmission. Forty-nine consecutive mothers infected with HCV who transmitted infection to their offspring and, as a control group, 557 consecutive mothers infected with HCV who did not transmit infection, together with their children and the fathers of the children who were also the sexual partners of the mothers were evaluated. History of intravenous drug use was significantly more frequent in women with partners infected with HCV than in women with partners not infected [115/180 (63.9%) vs. 87/401 (21.7%); relative risk (RR): 6.38, 95% confidence intervals (CI): 4.34-9.39, P < 10(-3)]. HCV infection was more frequent in the partners of mothers who transmitted perinatally HCV [23/49 (46.9%) vs. 174/557 (31.2%); RR: 1.95, 95%CI: 1.08-3.51, P = 0.03]. Multivariate analysis demonstrated that paternal HCV infection is not a risk factor per se for perinatal HCV transmission, but its role is dependent on maternal intravenous drug use [adjusted RR: 1.23 (95%CI: 0.44-3.39, P = 0.6)]. In conclusion, the present study shows that partners of mothers infected with HCV with a history of intravenous drug use were at a higher risk of HCV infection. HCV infection of the father seems to be associated with perinatal transmission but this relationship is dependent on maternal history of intravenous drug use. | 18,814,243 |
Interactions with nanoscale topography: adhesion quantification and signal transduction in cells of osteogenic and multipotent lineage. | Polymeric medical devices widely used in orthopedic surgery play key roles in fracture fixation and orthopedic implant design. Topographical modification and surface micro-roughness of these devices regulate cellular adhesion, a process fundamental in the initiation of osteoinduction and osteogenesis. Advances in fabrication techniques have evolved the field of surface modification; in particular, nanotechnology has allowed the development of nanoscale substrates for the investigation into cell-nanofeature interactions. In this study human osteoblasts (HOBs) were cultured on ordered nanoscale pits and random nano "craters" and "islands". Adhesion subtypes were quantified by immunofluorescent microscopy and cell-substrate interactions investigated via immuno-scanning electron microscopy. To investigate the effects of these substrates on cellular function 1.7 k microarray analysis was used to establish gene profiles of enriched STRO-1+ progenitor cell populations cultured on these nanotopographies. Nanotopographies affected the formation of adhesions on experimental substrates. Adhesion formation was prominent on planar control substrates and reduced on nanocrater and nanoisland topographies; nanopits, however, were shown to inhibit directly the formation of large adhesions. STRO-1+ progenitor cells cultured on experimental substrates revealed significant changes in genetic expression. This study implicates nanotopographical modification as a significant modulator of osteoblast adhesion and cellular function in mesenchymal populations. | 18,814,275 |
Modified Escherichia coli B (BL21), a superior producer of plasmid DNA compared with Escherichia coli K (DH5alpha). | Plasmid DNA (pDNA) is an emerging experimental vaccine, produced in E. coli, initially targeted for viral diseases. Unlike traditional protein vaccines whose average dose is micrograms, the average dose of pDNA is on the scale of milligrams. Production yields are, therefore, important for the future development of this vaccine. The E. coli strains currently used for pDNA production, JM109 and DH5alpha, are both suitable for production of stable pDNA due to the deletion of recA and endA, however, these two E. coli K strains are sensitive to growth conditions such as high glucose concentration. On the other hand E. coli BL21 is less sensitive to growth conditions than E. coli JM109 or DH5alpha, this strain grows to higher densities and due to its active glyoxylate shunt and anaplerotic pathways is not sensitive to high glucose concentration. This strain is used for recombinant protein production but not for pDNA production because of its inability to produce stable pDNA. To adapt E. coli BL21 for stable pDNA production, the strain was mutated by deleting both recA and endA, and a proper growth and production strategy was developed. Production values, reaching 2 g/L were obtained using glucose as a carbon source. The produced plasmid, which was constructed for HIV clinical study, was found to have identical properties to the plasmid currently produced by E. coli DH5alpha. | 18,814,292 |
Convective-diffusive mass transfer of agonist and the intracellular calcium response of endothelial cell. | Endothelial cell layer regulates several crucial physiological processes of the vascular system. The mechanism of the response of this cell layer to the flow of surrounding fluid is still largely unclear. In the present article, a comparison of the available experimental results for the intracellular calcium ion concentration and theoretical results for the extra-cellular ATP concentration obtained using a convective-diffusive mass transfer model, has been made which supports the mass transfer model for the endothelial cell response to the fluid flow. The experimental results are in excellent agreement with the calculated values assuming the effect of ATP concentration alone. | 18,814,294 |
Functional differentiation of a clone resembling embryonic cortical interneuron progenitors. | We have generated clones (L2.3 and RG3.6) of neural progenitors with radial glial properties from rat E14.5 cortex that differentiate into astrocytes, neurons, and oligodendrocytes. Here, we describe a different clone (L2.2) that gives rise exclusively to neurons, but not to glia. Neuronal differentiation of L2.2 cells was inhibited by bone morphogenic protein 2 (BMP2) and enhanced by Sonic Hedgehog (SHH) similar to cortical interneuron progenitors. Compared with L2.3, differentiating L2.2 cells expressed significantly higher levels of mRNAs for glutamate decarboxylases (GADs), DLX transcription factors, calretinin, calbindin, neuropeptide Y (NPY), and somatostatin. Increased levels of DLX-2, GADs, and calretinin proteins were confirmed upon differentiation. L2.2 cells differentiated into neurons that fired action potentials in vitro, and their electrophysiological differentiation was accelerated and more complete when cocultured with developing astroglial cells but not with conditioned medium from these cells. The combined results suggest that clone L2.2 resembles GABAergic interneuron progenitors in the developing forebrain. | 18,814,314 |
Molecular interactions of isoxazolcurcumin with human serum albumin: spectroscopic and molecular modeling studies. | Curcumin is a nontoxic natural product with diverse pharmacological potencies. We report the interaction of a potent synthetic derivative of curcumin, isoxazolcurcumin (IOC) with human serum albumin (HSA) using various biophysical methods. The observed fluorescence quenching of HSA by IOC is due to a complex formation by a static quenching process with a quenching constant of the order of 10(5) M(-1). The binding affinity and the number of binding sites were obtained from a Scatchard analysis. Thermodynamics reveals that the interaction is entropy driven with predominantly hydrophobic forces. From the observed Förster-type fluorescence resonance energy transfer (FRET), the donor (Trp 214 in HSA) to acceptor (IOC) distance is calculated to be 3.2 nm. The conformational changes of HSA due to the interaction were investigated qualitatively from synchronous fluorescence spectra along with a quantitative estimation of the secondary structure from Fourier Transform Infrared (FTIR) and circular dichroism (CD) spectroscopies. Molecular docking studies were performed to obtain information on the possible residues involved in the interaction process, and changes in accessible surface area of the interacting residues were calculated. The preferred binding site of IOC was analyzed by ligand displacement experiments with 1-anilino-8-naphthalenesulfonate (ANS) and warfarin-bound HSA. | 18,814,316 |
Proteomic analysis of alterations in the secretome of Arabidopsis thaliana suspension cells subjected to nutritional phosphate deficiency. | A proteomic approach was applied to compare the secretome (culture filtrate proteome) of phosphate-sufficient (+Pi) and Pi-deficient (-Pi) Arabidopsis thaliana suspension cell cultures. Secretomes harvested from the +Pi and -Pi cells yielded dissimilar 2-DE maps. PMF via MALDI-TOF MS resulted in the identification of 50 protein spots representing 37 discrete proteins having unique gene identities. A total of 24 Pi-starvation responsive proteins were identified, with 18 of these being up-regulated and six down-regulated. Secreted proteins up-regulated by the -Pi cells included a ribonuclease involved in Pi scavenging from extracellular nucleic acids, as well as enzymes of cell wall modification, proteolysis, pathogen responses, and ROS metabolism. Enzyme activity assays and immunoblotting demonstrated that a pair of purple acid phosphatase isoforms having subunit M(r)s of 65 and 55 kDa was also secreted by the -Pi cells. Semiquantitative RT-PCR was used to assess the relationship between mRNA levels and relative amounts of selected secretome proteins. The results indicate that transcriptional control is but one of many factors contributing to Arabidopsis Pi starvation responses, and highlight the importance of parallel biochemical/proteomic studies of -Pi plants. | 18,814,331 |
Parameatal urethral cyst. | Cyst formation in the parameatal area of the urethra is an uncommon entity. It was first reported in two male cases as recently as 1956 by Thompson and Lantin. Further reports have been rare. Herein, we report a case of a 21 year-old male having a spherical, cystic swelling 1 cm in size at the external urethral meatus. The diagnosis of parameatal urethral cyst was made and the cyst was excised. Histopathological examination revealed a monolocular cyst lined with transitional cells. The postoperative period was uneventful. | 18,814,338 |
Knowledge, beliefs and attitudes about HIV/AIDS-related issues, and the sources of knowledge among health care professionals in southern Nigeria. | The HIV/AIDS pandemic has become one of the most important public health problems in recent times and it is having a profound impact on the lives of infected people and their families. There is an acknowledged burden of HIV/AIDS in Nigeria. As the prevalence of HIV/AIDS infection rises, health care professionals worldwide can expect greater clinical exposure to infected patients. The care of people living with AIDS presents a significant challenge to the health care sector. This study seeks to explore the relationship between sources of HIV/AIDS information and knowledge, and the relationship between knowledge of HIV/AIDS and care for people with AIDS among health care providers in three different levels of health care institutions in the southern region of Nigeria. Health care workers from two states in southern Nigeria completed a questionnaire that was designed to assess knowledge, attitudes and practices about HIV/AIDS. The sample was composed of 277 (65%) females and 135 (31.7%) males. The results showed a fair level of knowledge among all health care professionals, with the highest level of knowledge among the doctors and the lowest among laboratory workers. There was a significant gender difference in the level of knowledge but the data suggested that knowledge did not differ by hospital settings. There were generally negative feelings and views about the care of HIV/AIDS patients among the professionals, these views being worst at the community health centers and best at the government hospital. The greatest source of information for the majority of professionals was health talks/seminars, and those respondents who got their information from school scored the highest on the items on general knowledge of HIV/AIDS incidence, cause, transmission, and clinical treatment. This has important implications for future interventions designed for health care professionals including doctors, nurses and laboratory workers. | 18,814,404 |
Workplace wellness programs in Canada: an exploration of key issues. | Faced with the reality of rising health costs, Canadian employers are thinking beyond traditional notions of responsibility for employee health and have begun to embrace Workplace Wellness Programs (WWPs). This article investigates the critical issues of WWPs in the Canadian context from the perspective of key stakeholders. Using a combination of literature and key informant interviews, seven key themes are presented along with recommendations for wider implementation of WWPs in Canada. | 18,814,425 |
Single parameter wrist ultrasonography as a first-line screening examination in suspected carpal tunnel syndrome patients. | Carpal tunnel syndrome (CTS) is the most common form of peripheral nerve entrapment. Electromyography with selected nerve conduction studies (NCS) is an accepted diagnostic tool in CTS patients. Ultrasonography presents a widely available and low cost investigation method and its position in CTS diagnostics needs further clarification with concrete recommendations for clinical practice. A prospective study of 37 patients with 74 wrists (59 wrists with suspected CTS) was done. Normative data were obtained from a control group of 25 healthy persons (50 wrists) age and sex matched. All persons underwent ultrasonographic examination (median nerve cross-sectional area at carpal tunnel entrance measurement--CSA) and median NCS studies (distal motor and sensory latency measurement--DML and DSL). CSA has a sensitivity of 93% (CI 84-97%) and specificity of 96% (CI 87-99%) in our patients group. Conventional first-line NCS studies results in our patients groupare as follows: DML sensitivity 58% (CI 45-69%) and specificity 100% (CI 93-100%); DSL sensitivity 88% (CI 78-94%) and specificity 94% (CI 84-98%). We recommend the use of single-parameter wrist ultrasonography as a first-line screening laboratory method in suspected CTS diagnosis (Ref. 14). Full Text (Free, PDF) www.bmj.sk. | 18,814,435 |
Prenatal exposure to acetaminophen and respiratory symptoms in the first year of life. | Prevalence of asthma in developed countries increased between the 1970s and the 1990s. One factor that might contribute to the trends in asthma is the increased use of acetaminophen vs aspirin in children and pregnant women. To examine relationships between in utero exposure to acetaminophen and incidence of respiratory symptoms in the first year of life. A total of 345 women were recruited in the first trimester of pregnancy and followed up with their children through the first year of life. Use of acetaminophen in pregnancy was determined by questionnaire and related to incidence of respiratory symptoms. Use of acetaminophen in middle to late but not early pregnancy was significantly related to wheezing (odd ratio, 1.8; 95% confidence interval, 1.1-3.0) and to wheezing that disturbed sleep (odds ratio, 2.1; 95% confidence interval, 1.1-3.8) in the first year of life after control for potential confounders. This study suggests that use of acetaminophen in middle to late but not early pregnancy may be related to respiratory symptoms in the first year of life. Additional follow-up will examine relationships of maternal and early childhood use of acetaminophen with incidence of asthma at ages 3 to 5 years, when asthma diagnosis is more firmly established. | 18,814,450 |
Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma. | Specific immunotherapy is the only potentially curative treatment in patients with allergic rhinitis and allergic asthma. Health economic evaluations on this treatment, particularly in a German context, are sparse. To evaluate the cost-effectiveness of specific subcutaneous immunotherapy (SCIT) in addition to symptomatic treatment (ST) compared with ST alone in a German health care setting. The analysis was performed as a health economic model calculation based on Markov models. In addition, we performed a concomitant expert board composed of allergy experts in pediatrics, dermatology, pneumology, and otolaryngology. The primary perspective of the study was societal. Additional sensitivity analyses were performed to prove our results for robustness. The SCIT and ST combination was associated with annual cost savings of Euro140 per patient. After 10 years of disease duration, SCIT and ST reach the breakeven point. The overall incremental cost-effectiveness ratio (ICER) was Euro-19,787 per quality-adjusted life-year (QALY), with a range that depended on patient age (adults, Euro-22,196; adolescents, Euro-14,747; children, Euro-12,750). From a third-party payer's perspective, SCIT was associated with slightly additional costs. Thus, the resulting ICER was Euro8,308 per QALY for all patients. Additional SCIT was associated with improved medical outcomes and cost savings compared with symptomatic treatment alone according to a societal perspective. Taking a European accepted ICER threshold of up to Euro50,000 per QALY into account, additional SCIT is considered clearly cost-effective compared with routine care in Germany. The degree of cost-effectiveness is strongly affected by costs related to SCIT and the target population receiving such treatment. | 18,814,456 |
Basic science for the practicing physician: gene expression microarrays. | To provide a general overview of gene expression microarray technology and its relevance to physicians practicing allergy/immunology. The PubMed interface to MEDLINE was searched for primary and review articles on gene expression microarrays. Specific articles on clinical applications of microarrays were retrieved, along with articles on use of microarrays in models of allergy, asthma, and immunologic diseases. The author's knowledge of the field was used to include sources of information other than those obtained through the MEDLINE search. A synopsis of gene expression microarray technology, with emphasis on the relevance to allergy, asthma, and immunology, is presented. Gene expression microarray technology allows investigators to measure gene expression across the genome. This has allowed researchers to improve our understanding of immunologic mechanisms in disease models. Initially used solely as a research tool, microarray-based clinical tests are now available, and many more are in development. Use of microarrays in allergy, asthma, and immunology will support the development of novel diagnostic tests for the physician and facilitate exploration of the basic mechanisms underlying allergic and immunologic diseases. | 18,814,457 |
Depth of facial expression processing depends on stimulus visibility: behavioral and electrophysiological evidence of priming effects. | Participants performed a priming task during which emotional faces served as prime stimuli and emotional words served as targets. Prime-target pairs were congruent or incongruent, and two levels of prime visibility were obtained by varying the duration of the masked primes. To probe a neural signature of the impact of the masked primes, lateralized readiness potentials (LRPs) were recorded over motor cortex. In the high-visibility condition, responses to word targets were faster when the prime-target pairs were congruent than when they were incongruent, providing evidence of priming effects. In line with the behavioral results, the electrophysiological data showed that high-visibility face primes resulted in LRP differences between congruent and incongruent trials, suggesting that prime stimuli initiated motor preparation. Contrary to the above pattern, no evidence for reaction time or LRP differences was observed in the low-visibility condition, revealing that the depth of facial expression processing is dependent on stimulus visibility. | 18,814,465 |
Venous access in oncology and haematology patients: Part two. | To assess the validity and inter-rater reliability of two tools, Venous Assessment Tool (VAT) and Deciding on IntraVenous Access (DIVA), using thematic analysis of feedback from nurses who used the tools, Analysis methods used in grounded theory were employed to investigate the written feedback provided by nurses. Inter-rater reliability was tested statistically using percentage agreement and the kappa (K) statistic. Thematic analysis of the nurses' feedback generated themes concerning the role of clinical judgement, how theory translates to practice and the role of patient preference when using VAT and DIVA. Exploring these themes confirmed the validity of the tools and highlighted the importance of these considerations when evaluating the usefulness of assessment tools in the clinical environment. When VAT was used by a group of nurses to assess patients, the strength of agreement statistically was 'moderate'. When using DIVA, the tool demonstrated 'very good' agreement statistically. When used with oncology and haematology patients, VAT and DIVA have been shown to generate agreement among the nurses who used them beyond that which would be expected by chance. As the only tools of this kind with evidence of inter-rater reliability, they provide clinicians with a useful resource which can be used in practice or research. However, the use of assessment tools cannot replace clinical judgement or override the preferences of patients. | 18,814,475 |
[Lucentis versus Avastin--is there a light at the end of the tunnel for age-related macular degeneration patients?]. | Age-related macular degeneration is the leading cause of blindness and visual impairment in the developed world. The recently introduced anti-vascular endothelial growth factor (VEGF) intravitreal injections of Ranibizumab (Lucentis) and Bevacizumab (Avastin) generated a heated academic argument: on the one hand Lucentis is the only drug that was proven effective and relatively safe in large prospective double-blinded studies, albeit this drug is expensive and might cost up to $1000 per single injection. On the other hand, Avastin is widely used worldwide as a low cost alternative for Lucentis, with an estimated cost of about $120 per injection, although its efficacy and side effects were investigated only in smaller retrospective studies. The ophthalmic community still lacks definite information regarding which is the preferred drug, and awaits the results of a large prospective study comparing the two drugs. | 18,814,519 |
[Cancer-related lymphedema in Israel]. | Lymphedema, the accumulation of protein-rich fluid in an involved extremity or other body part, is a chronic life-long condition following many types of surgical procedures, most often breast cancer surgical therapy. The patient suffering from lymphedema faces difficult medical, social, psychological and aesthetic issues. The incidence of lymphedema after modern breast cancer surgical treatment has been reported for between 5 to 56% of patients. Taking into account the incidence of breast cancer in Israel, there could be a yearly incidence of over 1000 new patients per year in Israel suffering from arm lymphedema. The authors reviewed the literature concerning epidemiology, pathophysiology, risk factors, diagnosis and treatment strategy. In addition, some insights were provided regarding lymphedema treatment in Israel. This review aims to improve the awareness and knowledge of physicians and other health care professionals on this treatable but often forgotten condition. | 18,814,523 |
[Anxiety disorders in children and adolescents]. | Anxiety disorders are the most common psychiatric illnesses in children and adolescents. They are associated with significant distress and impairment. Most of the children and adolescents with anxiety disorders are not detected and only a minority receives adequate treatment. Anxious children and adolescents often follow a chronic course of disease with elevated risk of depressive disorders, substance abuse and even suicide. Risk factors for anxiety disorders are complex and consist of intricate interplay of multiple factors, including genetic makeup and environmental risks. Effective, evidence-based treatments for anxiety disorders in children and adolescents consist of cognitive-behavioral therapy and pharmacotherapy with serotonin specific reuptake inhibitors. Further research is needed to design high-quality screening tools for anxiety disorders in the primary care setting. | 18,814,524 |
Factors influencing the use of episiotomy during vaginal delivery in South Eastern Nigeria. | Given considerable evidence that routine episiotomy increases maternal morbidity and without evidence to support maternal or neonatal benefit, has episiotomy use changed among health care providers? To date, very limited information exists relating to the past and current practice of episiotomy in many developing countries. To determine the prevalence of episiotomy at Aba in South Eastern Nigeria, examine factors influencing the performance of episiotomy and document complications associated with the procedure. A hospital based retrospective study. The Abia State University Teaching Hospital (ABSUTH), Aba in South Eastern Nigeria, from January 2001 to December 2005. Four thousand, one hundred and seventy two mothers who delivered vaginally within the study period. There were 1877 episiotomies, for an episiotomy rate of 45%. Ninety per cent of the primigravid parturients had episiotomy. Women undergoing episiotomy were younger (mean age 24.7 years; range 16-37) than women without episiotomy (mean age 28.5 years, range 20-43). When controlled for parity and maternal age, other risk factors were occipito-posterior position, vacuum extraction, forceps delivery, vaginal breech delivery, and a history of Caesarean section. Episiotomy use was also associated with major perineal lacerations and increased length of hospital stay. The episiotomy rate of 45 per 100 vaginal deliveries in this study is obviously higher than evidence-based recommendations for optimal patient care. A policy of systematic reduction in the incidence of episiotomy can be pursued in this hospital. Greater attention needs to be paid to selection of women to undergo episiotomy. | 18,814,534 |
Myxidium scripta n. sp. identified in urinary and biliary tract of Louisiana-farmed red-eared slider turtles Trachemys scripta elegans. | During a necropsy investigation of a mortality event occurring at a turtle farm in Assumption Parish, Louisiana, spores of a myxozoan were identified in the renal tubules in 3 of 6, the gall bladder lumen in 2 of 6, and the bile ductule in 1 of 6 red eared slider turtles Trachemys scripta elegans. In total, myxozoa were identified in 4 of 6 turtles. In 1 turtle, renal tubules contained numerous mature spores, had epithelial hyperplasia, granulomatous transformation, compression of adjacent tubules and interstitial lymphocytic nephritis. The genus of myxozoan was Myxidium, based on spore morphology in cytological preparations, in histologic section, and by electron microscopy. In cytological preparation the spores had mean dimensions of 18.8 x 5.1 microm and a mean polar capsule dimension of 6.6 x 3.5 microm. Electron microscopy showed renal tubules contained plasmodia with disporoblasts with spores in various stages of maturation. Ultrastructure of mature spores demonstrated a capsule containing 2 asymmetrical overlapping valves and polar capsules containing a polar filament coiled 6 to 8 times and surrounded by a membrane composed of a double layer wall. The small subunit rDNA gene sequence was distinct from all other Myxidium species for which sequences are available. Additionally, this is the first Myxidium species recovered from a North American chelonian to receive genetic analysis. Although T. s. elegans is listed as a host for Myxidium chelonarum, this newly described species of Myxidium possessed larger spores with tapered ends; thus, we described it as a new species, Myxidium scripta n. sp. This report documents a clinically significant nephropathy and genetic sequence from a Myxidium parasite affecting a freshwater turtle species in North America. | 18,814,545 |
Gambling: normal adolescent activity or pathologic addiction? | A 15-year-old comes to the school counselor. He owes $4,000 in gambling debts to a sports-betting bookie, and he doesn't have the money. He is afraid. Yet, 2 weeks later, he bet on the Super Bowl and won $3,000. A 14-year-old limits his betting to $20 and $30; he only bets what he has and he is happy with his successes. A 17-year-old was born with a malformed arm and cannot play sports; instead, he makes bets on sports games. He sells his belongings to get the money he needs; right now, he owes $700. Are the behaviors of these teens unusual? | 18,814,567 |
Ethical perspectives of children's assent for research participation: deontology and on utilitarianism. | Is a child's assent to participate in research that does not have the potential to directly benefit the child ethically mandated? Analysis of this particular dilemma of health care research in children using two competing theories results in different answers. Deontology (principle-based ethics) will be contrasted with utilitarianism (consequentialism). Historical cases of research with children will be used as exemplars of these two theoretical positions. | 18,814,566 |
Horizontal distribution and levels of heavy metals in the biggest snowstorm in a century in Shenyang, China. | The horizontal distribution and levels of heavy metals in the biggest snowstorm in Shenyang since 1904 were investigated by analyzing 4 metals (As, Cd, Pb, and Cu) in a series of ultraclean samples collected from 17 sites distributed in different regions of the Shenyang area, China. The results showed that the concentrations of all the 4 heavy metals in snow from the industrial regions were high, up to 7.3 (As), 2.2 (Cd), 850.0 (Pb), and 0.197-20.2 (Cu) microg/kg, respectively. In the suburb, in contrast, their concentrations were not detected, except for As. Because of the long-term application of arsenical pesticides and herbicides, As was detected in the snow samples which collected on the farm. As, Cd, and Pb were also detected in the snow samples collected from the parks, the residential areas, and the commercial districts mainly by reason of human activities. In a sense, long-term industrial activities, traffic activities, coal combustion, and agricultural activities affected the horizontal distribution and levels of these heavy metals in snow differently. The data relating to the horizontal distribution and concentrations of heavy metals in the snow under extreme climatic conditions can provide with a unique snapshot of environmental pollution situation and behaviors in urban areas. | 18,814,581 |
Location and PCR analysis of catabolic genes in a novel Streptomyces sp. DUT_AHX capable of degrading nitrobenzene. | A novel strain of Streptomyces sp. DUT_AHX was isolated from sludge contaminated with nitrobenzene and identified on the basis of physiological and biochemical tests and 16S ribosomal DNA (rDNA) sequence analysis. The optimal degradation conditions were as follows: temperature 30 degrees C, pH 7.0-8.0, shaking speed 150-180 r/min, and inocula 10% (V/V). The strain, which possessed a partial reductive pathway with the release of ammonia, was also able to grow on mineral salts basal (MSB) medium plates with 2-aminophenol, phenol, or toluene as the sole carbon source. Furthermore, the enzyme activity tests showed crude extracts of nitrobenzene-grown DUTAHX contained 2-aminophenol 1,6-dioxygenase activity. The 17-kb plasmid was isolated by the modified alkaline lysis method and was further cured by sodium dodecyl sulphate (SDS) together with 37 degrees C. As a result, the cured derivative strain DUTAHX-4 lost the 2-aminophenol 1,6-dioxygenase activity. The results suggested that the catabolic genes encoding the nitrobenzene-degrading enzymes were plasmid-associated. Moreover, the plasmid DNA was amplified with degenerate primers by touchdown PCR and an expected size fragment (471 bp) was generated. The Blast results revealed that the gene encoding a 157 amino acid polypeptide was 39%-76% identical to YHS domain protein. The further examination of the plasmid would demonstrate the molecular basis of nitrobenzene catabolism in Streptomyces, such as regulation and genetic organization of the catabolic genes. | 18,814,584 |
Combined team training. | For professions that operate in dynarnic environments, developing and improving team performance is a significant issue. Paramedics often utilize advanced, high-risk, low-frequency clinical procedures such as endotracheal intubation, rapid sequence induction, needle chest decompression and surgical airways. These procedures are performed in a team environment alongside EMTs and first responders. Though these groups (paramedics and EMTs/first responders) operate together on scenes, if they come from different organizations, they may rarely train together. By combining the training they receive, each of these groups can improve their cybernation, or the high degree of preparedness and skill achieved when a team performs its individual and collective tasks not only correctly, but also with the rapid and smooth automaticity that's the hallmark of high-performance teams. | 18,814,639 |
Environmental parameters affecting the species diversity along the Aliakmon River, North Greece. | The annual distribution of aquatic and coastal macrophytes in five selected sites along the Aliakmon River was studied from January 2005 to December 2005 in Northern Greece. Soil and water chemical parameters in these sites were also evaluated. A total of 75 taxa were recorded belonging to 37 families and 53 genera. The majority of the macrophytes belonged to coastal plants (76%), whereas the rest of the macrophytes belonged to aquatic plants (24%). Species of the family Asteraceae were dominant among coastal plants, whereas species of the family Potamogetonaceae were dominant among aquatic plants. Soil samples from the site of Dam of Veria had higher pH and electric conductivity (80-100 cm depth), whereas CaCO3 contents were significantly higher in soil samples from the area of P. Prodromos (60-80 cm depth). Most physicochemical water parameters as well as selected soil nutrients and major ionic components showed an increase during the low charge period (fall) compared to with the high charge period (spring), especially in parameters associated with agricultural activity. Furthermore, there was an increase in most examined values moving towards the delta of the river. | 18,814,647 |
Abiotic transmission of Rice yellow mottle virus through soil and contact between plants. | The roles of guttation fluid, irrigation water, contact between plants and transplantation into contaminated soil in the transmission of Rice yellow mottle virus (RYMV) were assessed. RYMV presence and infectivity were tested by Enzyme-Linked Immunosorbent Assay (ELISA) and by inoculation to susceptible rice cultivar BG90-2. The virus was readily detected in guttation fluid collected from infected rice plants. Transmission tests from this fluid led to high disease incidence (86.6%). Irrigation water collected at the base of infected plants growing in pots was less infectious, as inoculations led to disease incidences below 40%. No virus was detected and could be transmitted from field-irrigation water. Up to 44% healthy rice plants whose leaves were in contact with those of infected plants became infected but, no transmission occurred through intertwined roots. Transplantation of rice seedling into virus-contaminated soil also led to plant infection. However, virus survival in the soil decrease rapidly and infectivity was completely lost 14 days after soil contamination. Altogether, these results indicated that high planting densities of rice are likely to favour secondary spread of rice yellow mottle disease. Transplantation of rice seedlings not earlier than 2 weeks after soil preparation should prevent soil transmission of the virus. Although guttation fluid is highly infectious its contribution to virus infectivity in irrigation water is negligible as field-irrigation water was not found to be an infectious source for RYMV. | 18,814,653 |
Prevalence of hypertension among Iranian hemodialysis patients and associated risk factors: a nationwide multicenter study. | The aim of this study is to document the prevalence of HTN and characterize risk factors associated with HTN in Iranian hemodialysis patients. Three hundred and thirty seven HD patients from 5 university based HD centers around Iran were enrolled in the study. Urea reduction ratio was calculated using formula: 100 * (1-(urea before HD/urea after HD)). Pearson Chi-square test, independent sample t-test and one way ANOVA were used for evaluations, where appropriate. Multivariate logistic regression model was used for defining independent risk factors. Two sided p < 0.05 were considered significant. Patients with diabetes mellitus and hypertension as causes of ESRD significantly were more likely to have hypertension before and after dialysis (p < 0.05). Patients with conventional thrice weekly dialysis (compared to twice), hemodialysis duration of more that 6 months, acetate type of dialysate, ESRD cause when diabetes mellitus and hypertension, were significantly associated with having pre-HD hypertension. We also found that hemodialysis center of the capital city had a significant better measures compared to other cities (p < 0.05). This study revealed a relatively acceptable prevalence of hypertension in our HD population. Nevertheless, because of higher prevalence of HTN in HD centers out of capital city, it seems necessary that we should urgently pay more attention in promotion of these centers toward achieving better outcome with implementing strict guidelines to follow. | 18,814,655 |
Pregnancy rate following transfer of in vitro produced lamb derived embryos in two embryonic stages. | Ovine embryos were produced by maturation, fertilization and in vitro culture (IVM/IVF/IVC) of oocytes collected from slaughtered prepubertal ewes. At 24 h post IVM, oocytes were fertilized with fresh semen collected from Lori-Bakhtiari breed at a concentration of 1.0 x l0(6) sperm mL(-1). The presumptive ova/embryos were transferred into the embryo culture medium at 22-24 h post IVF. Following 4 to 7 day in culture, embryos (at morula and blastocyst stage, respectively) were transferred surgically to the uterine horn of synchronized recipients. Pregnancy was diagnosed at day 30 by hormonal assay and at days 55 and 140 of gestation by ultrasonography and pregnancies were allowed to go to term. A total of nine ewes received 27 embryos (3 embryos/ewe). Five ewes received 15 embryos at morula stage and four ewes received 12 embryos at blastocyst stage. From those received morula stage embryos one was pregnant on day 30 (20%), though no pregnancy was diagnosed on each of days 55 and 140. While from those received blastocyst stage embryos, three ewes were pregnant on day 30 (75%) and two ewes (50%) remained pregnant on each of days 55 and 140. In conclusion, day 4 IVM-IVF morula stage embryos had a lower survival rate than did day 7 IVM-IVF blastocysts embryos, following transfer to the synchronized recipient ewes. | 18,814,661 |
Callogenic studies of Achyranthes aspera leaf explant at different hormonal combinations. | With the objective to promote in vitro callus induction, leaf segments of Achyranthes aspera were inoculated on basal MS medium supplemented with 3.0% sucrose and 0.8% agar with different concentrations of 2,4-D alone and in combination with NAA, BAP, IAA, IBA and Zeatin. The explants were maintained in growth room at 25 +/- 1 degrees C and 16 h light cycle. The best callus induction was obtained with 2,4-D (1.0 and 2.0 mg L(-l)) in combination with NAA (0.5 mg L(-1)). Callus induction and good texture from leaf explant was also observed at 2,4-D with BAP. On these combinations morphologically, light green, soft, compact and non-embryogenic callus (Type III callus) was observed. While morphology of callus and callogenic response was poor at 2,4-D alone or in combination with other hormones at different concentrations. | 18,814,664 |
Backbreaking work. What you need to know about lifting and back safety in EMS. | Geraldine did not look very heavy, but she was wedged between the toilet and bath-tub. She had slipped while getting out of the tub and was complaining of severe hip pain. The room was only big enough for me, my partner and Geraldine, who needed to be lifted up and out of the room to the cot in the hallway. The question at hand was how to keep Geraldine as pain-free as possible while protecting our own backs during the lift and move. Nearly every patient contact involves lifting and carrying equipment and patients, which applies forces that can potentially injure your back. In this article, we explore lifting and back safety for EMS providers. | 18,814,673 |
Cellular and molecular interactions between the apicomplexan parasites Plasmodium and Theileria and their host cells. | Apicomplexan parasites of the genera Theileria and Plasmodium have complicated life cycles including infection of a vertebrate intermediate host and an arthropod definitive host. As the Plasmodium parasite progresses through its life cycle, it enters a number of different cell types, both in its mammalian and mosquito hosts. The fate of these cells varies greatly, as do the parasite and host molecules involved in parasite-host interactions. In mammals, Plasmodium parasites infect hepatocytes and erythrocytes whereas Theileria infects ruminant leukocytes and erythrocytes. Survival of Plasmodium-infected hepatocytes and Theileria-infected leukocytes depends on parasite-mediated inhibition of host cell apoptosis but only Theileria-infected cells exhibit a fully transformed phenotype. As the development of both parasites progresses towards the merozoite stage, the parasites no longer promote the survival of the host cell and the infected cell is finally destroyed to release merozoites. In this review we describe similarities and differences of parasite-host cell interactions in Plasmodium-infected hepatocytes and Theileria-infected leukocytes and compare the observed phenotypes to other parasite stages interacting with host cells. | 18,814,683 |
Pathophysiology of enteric infections with Giardia duodenalius. | Giardia is the most prevalent human intestinal parasitic protist in the world, and one of the most common parasite of companion animals and young livestock. Giardia is a major cause of diarrhea in children and in travelers. The host-microbial interactions that govern the outcome of infection remain incompletely understood. Findings available to date indicate that the infection causes diarrhea via a combination of intestinal malabsorption and hypersecretion. Malabsorption and maldigestion mainly result from a diffuse shortening of epithelial microvilli. This enterocytic injury is mediated by activated host T lymphocytes. Pathophysiological activation of lymphocytes is secondary to Giardia-induced disruption of epithelial tight junctions, which in turn increases intestinal permeability. Loss of epithelial barrier function is a result of Giardia-induced enterocyte apoptosis. Recent findings suggest that these effects may facilitate the development of chronic enteric disorders, including inflammatory bowel disease, irritable bowel syndrome, and allergies, via mechanisms that remain poorly understood. A newly discovered SGLT-1 glucose uptake-mediated host cytoprotective mechanism may represent an effective modulator of the epithelial apoptosis induced by this parasite, and, possibly, by other enteropathogens. A better understanding of the pathogenesis of giardiasis will shed light on new potential therapeutic targets. | 18,814,692 |
Penetration of Trichobilharzia cercariae into mammals: dangerous or negligible event? | Bird schistosomes and cases of human cercarial dermatitis occur worldwide, but the number of cases is not monitored. Experiments with two schistosomes, namely Trichobilharzia szidati and T. regenti, show that they possess potent tools to penetration bird and mammalian skin, as well as exhibit species-specific migration patterns within vertebrate bodies. Therefore, the infections may affect different organs/tissues e.g. lungs or spinal cord. In this minireview, the adaptations and pathogenic effects of bird schistosomes in experimental mammals are discussed, and some ideas/hypotheses on risks to humans from exposure to bird schistosome cercariae are expressed. | 18,814,698 |
Environmental parasitology. Interactions between parasites and pollutants in the aquatic environment. | In recent years there has been an increasing number of papers showing how parasitism and pollution can interact with each other in aquatic organisms. Among the variety of investigated aspects especially the combined effects of pollution and simultaneous infection on the health of aquatic hosts (molluscs, crustaceans, fish, mammals) is of considerable interest. Effects of pollution on the occurrence and distribution of parasites is another interesting field of "Environmental Parasitology" attracting increasing attention. This mini-review presents some promising examples of interdisciplinary studies paying attention to the fact that under natural conditions no organism will only be affected by either parasites or pollution. | 18,814,718 |
Parasite co-structure: broad and local scale approaches. | A co-structure study is a comparison of demographic and/or genetic structure between two or more species. Such a comparative analysis among a parasite and its host(s) or among multiple parasite species is useful to elucidate factors that shape genetic variation within and among parasite populations. I provide a brief review of how co-structure studies in parasite systems can be used to address ecological, evolutionary, and epidemiological questions. Subjects that can be addressed with parasite costructure studies range from broad-scale analyses that compare phylogeographical patterns to local scale analyses that examine among host transmission within a host population. | 18,814,719 |
The population genetic structure of vectors and our understanding of disease epidemiology. | Understanding and predicting disease epidemiology relies on clear knowledge about the basic biology of the organisms involved. Despite the key role that arthropod vectors play in disease dynamics and detailed mechanistic work on the vector-pathogen interface, little information is often available about how these populations function under natural conditions. Population genetic studies can help fill this void by providing information about the taxonomic status of species, the spatial limits of populations, and the nature of gene flow among populations. Here, I briefly review different types of population genetic structure and some recent examples of where this information has provided key elements for understanding pathogen transmission in tick-borne systems. | 18,814,720 |
Manson's triple error. | The author discusses the significance, implications and limitations of Manson's work. How did Patrick Manson resolve some of the major problems raised by the filarial worm life cycle? The Amoy physician showed that circulating embryos could only leave the blood via the percutaneous route, thereby requiring a bloodsucking insect. The discovery of a new autonomous, airborne, active host undoubtedly had a considerable impact on the history of parasitology, but the way in which Manson formulated and solved the problem of the transfer of filarial worms from the body of the mosquito to man resulted in failure. This article shows how the epistemological transformation operated by Manson was indissociably related to a series of errors and how a major breakthrough can be the result of a series of false proposals and, consequently, that the history of truth often involves a history of error. | 18,814,729 |
[What is the purpose of dual or triple inhibition of the renin-angiotensin-aldosterone system?]. | The blockade of the renin-angiotensin-aldosterone system (RAAS) is helpful in the management of arterial hypertension, congestive heart failure, post-myocardial infarction and diabetic nephropathy. Such blockade can be obtained with an angiotensin converting enzyme inhibitor, a specific antagonist of angiotensin II AT1 receptors, an aldosterone receptor antagonist and/or a direct inhibitor of renin such as aliskiren. Various studies have demonstrated that a dual or even triple RAAS inhibition may offer a better cardiorenal protection, in refractory congestive heart failure and in nephropathy with proteinuria. However, in the ONTARGET study, the dual inhibition with ramipril plus telmisartan did not provide any additional benefit compared to ramipril alone in high-risk cardiovascular patients, but showed a worse tolerance profile. | 18,814,762 |
[CB1 receptor inhibition and glucose metabolism: role of rimonabant in type 2 diabetes]. | Endocannabinoid system is overactivated in individuals with abdominal obesity. CBI receptors, first individualized in the brain, are also expressed in the adipocyte, the skeletal muscle, the liver, the gut, and the pancreas. Their blockade improves glucose tolerance and lipid profile, thanks increased insulin sensitivity and adiponectin levels. Rimonabant, a selective antagonist of CBI receptors, improves glucose control in patients with type 2 diabetes, treated with diet alone, metformin, sulfonylurea or insulin, while it also reduces body weight and other risk factors. Ongoing studies aim at further demonstrating the potential of rimonabant in the management of type 2 diabetes, in the prevention of type 2 diabetes and in the protection against cardiovascular complications in (diabetic) patients with abdominal obesity. | 18,814,765 |
[Clinical effects of biapenem on febrile neutropenia in patients with hematological malignancy]. | Recent advances in the treatment of hematological malignancies often induce febrile neutropenia (FN) due to severe myelosuppression. The aim of this study was to evaluate the safety and efficacy of biapenem in such FN. Candidate patients were admitted to our hospital and were treat of their hematological malignancy from February 2005 to March 2006. They gave written informed consent to enter this study in advance. When the diagnosis of FN was established among them, those patients received intravenous biapenem 0.6 g every 12 hours. This trail was approved by our institutional review board. A total of 54 consecutive patients were registered and 49 patients were evaluable for response. The median age was 61. The underlying diseases were acute lymphocytic leukemia in 6 cases, acute myelocytic leukemia in 21, multiple myeloma in 3, and non-Hodgkin's lymphoma in 19. The response rate was 78% (excellent response: 51%, good response: 27%, minor response: 6%, no response: 16%). In patients with neutrophil counts under 500/microl, the response rate was 73%. Infectious death or other serious adverse events were not observed. Biapenem is effective and safe for treating FN. | 18,814,798 |
New developments in anticoagulation for atrial fibrillation. | The incidence of stroke in patients with atrial fibrillation (AF) is five times greater than that in age-matched controls. Warfarin reduces this incidence by two thirds and is the most effective agent for this indication. However, despite its efficacy, warfarin management is tedious and is useful only in a subsegment of the population who needs anticoagulation and has no contraindications. Many agents are poised to replace warfarin as an effective anticoagulant for stroke prevention in AF. The direct thrombin inhibitor dabigatran is furthest along in clinical development, followed by the factor Xa inhibitors rivaroxaban and apixaban. All these agents seem effective, and none appears mechanistically superior over another. Dabigatran's advantage is that it was tested in two dosages in a phase 3 evaluation based on earlier phase 2 studies in patients with AF, whereas dosage data for the other agents were extrapolated from phase 2 programs for venous thromboembolism prevention. The vitamin K antagonist ATI-5923 offers clinical benefits similar to warfarin's, but with no or fewer drug-drug interactions, potentially greater time in therapeutic range, and probably less need for dose adjustment and laboratory monitoring. It challenges the newer mechanistic agents in efficacy and raises the bar for comparison in future head-to-head trials. Further analysis and clinical trial testing are still needed to determine whether one or all of these agents are effective anticoagulants for stroke prevention in patients with AF. | 18,814,828 |
Dynamic transition of Dnmt3b expression in mouse pre- and early post-implantation embryos. | The de novo DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the creation of DNA methylation patterns in mouse development. Dnmt3b is more highly expressed in early developmental stages than Dnmt3a, and is thought to have an important role in the epigenetic gene regulation during early embryogenesis. Previous reports suggest that Dnmt3b is expressed preferentially in the embryonic lineage, but less in the extra-embryonic lineage, in early post-implantation embryos. However, it is unclear when this lineage-specific differential expression is established. Here we demonstrate that Dnmt3b shows a dynamic expression change during pre- and early post-implantation development. Contrary to the expectation, Dnmt3b is preferentially expressed in the trophectoderm rather than the inner cell mass at the mid blastocyst stage. Subsequently, the spatial Dnmt3b expression gradually changes during pre- and early post-implantation development, and finally Dnmt3b expression is settled in the embryonic lineage at the epiblast stage. The findings are consistent with the role for Dnmt3b in cell-lineage specification and the creation of lineage-specific DNA methylation patterns. | 18,814,855 |
Improved odor sensitivity in attention-deficit/hyperactivity disorder. | Deficits in olfactory function are common features in neurodegenerative and neuropsychiatric disorders. In Parkinson's disease, olfactory deficits were found in up to 90% of patients, and there is evidence for dopaminergic dysfunction underlying these deficits. Because of the involvement of the dopamine system in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), olfactory function was investigated in children with the disorder. We assessed odor threshold, identification, and discrimination in 20 children and adolescents with ADHD without medication, 20 patients with ADHD treated with methylphenidate, and 20 healthy control subjects matched for IQ, age, and sex. Odor sensitivity was higher (lower threshold) in ADHD patients without medication than in healthy control subjects (p < .004; Cohen's d = 1.273), whereas medicated patients did not differ significantly from healthy control subjects. No significant differences between groups with regard to odor discrimination or identification were detected. Selectively improved odor sensitivity in children with ADHD is reported for the first time, whereas odor discrimination and identification were unaffected. Stimulant medication normalized the odor sensitivity threshold. It is proposed that dopaminergic dysregulation is involved in this phenomenon. | 18,814,862 |
Improved method for fatty acid analysis in herbage based on direct transesterification followed by solid-phase extraction. | Direct transesterification (DT) and solvent extraction with acid or basic derivatization procedure for fatty acid (FA) analysis in herbage were compared. The highest total FA, alpha-linolenic and linoleic acid contents were obtained with DT. However, DT also produced the highest amount of interfering compounds, identified as phytadienes and sugar derivative products, which may co-elute with FA. An additional step based on solid-phase extraction to produce clean samples was proposed. This procedure is simple and gives good recoveries for the FA fortified samples. Additionally, structural characterization of 16:1 trans-3 was conducted by covalent adduct chemical ionization tandem mass spectrometry. | 18,814,883 |
Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2. | Cholesterol present in the plasma membrane of target cells has been shown to be important for the infection by SARS-CoV. We show that cholesterol depletion by treatment with methyl-beta-cyclodextrin (m beta CD) affects infection by SARS-CoV to the same extent as infection by vesicular stomatitis virus-based pseudotypes containing the surface glycoprotein S of SARS-CoV (VSV-Delta G-S). Therefore, the role of cholesterol for SARS-CoV infection can be assigned to the S protein and is unaffected by other coronavirus proteins. There have been contradictory reports whether or not angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV, is present in detergent-resistant membrane domains. We found that ACE2 of both Vero E6 and Caco-2 cells co-purifies with marker proteins of detergent-resistant membranes supporting the notion that cholesterol-rich microdomains provide a platform facilitating the efficient interaction of the S protein with the cellular receptor ACE2. To understand the involvement of cholesterol in the initial steps of the viral life cycle, we applied a cell-based binding assay with cells expressing the S protein and cells containing angiotensin-converting enzyme 2 (ACE2). Alternatively, we used a soluble S protein as interaction partner. Depletion of cholesterol from the ACE2-expressing cells reduced the binding of S-expressing cells by 50% whereas the binding of soluble S protein was not affected. This result suggests that optimal infection requires a multivalent interaction between viral attachment protein and cellular receptors. | 18,814,896 |
Treatment of PAHs in contaminated soil by extraction with aqueous DNA followed by biodegradation with a pure culture of Sphingomonas sp. | The biodegradation of polycyclic aromatic hydrocarbons (PAHs) in aqueous deoxyribonucleic acid (DNA) solution from contaminated soil washing was investigated. Initial data with a model effluent consisting of anthracene, phenanthrene, pyrene and benzo[a]pyrene that were individually dissolved in 1% aqueous DNA solution confirmed their positive degradation by Sphingomonas sp. at around 10(8)CFU mL(-1) initial cell loading. For anthracene and phenanthrene, complete removal was achieved within 1h treatment. Degradation of pyrene and benzo[a]pyrene took a relatively longer time of a few days and weeks, respectively. DNA-dissolved PAHs were also degraded relatively faster than PAH crystals in aqueous medium to suggest that the binding of the PAHs in the polymer does not pose serious constraint to bacterial uptake. The DNA was stable against the PAH-degrading bacteria. Parallel experiments with actual DNA solutions obtained during pyrene extraction from an artificially spiked soil also showed similar results. Close to 100% pyrene degradation was achieved after 1d treatment. With its chemical stability, the cell-treated DNA was re-used up to four cycles without a considerable decline in extraction performance. | 18,814,900 |
Concentrations and fluxes of dissolved organic carbon in UK topsoils. | Dissolved organic carbon (DOC) concentrations in soil water samples collected from depths of 5 to 20 cm at 10 moorland and 11 forest sites during the period 2000-2006 were obtained from new measurements and from the monitoring programmes of the UK Environmental Change Network and the International Cooperative Programme (ICP) on Forests. Data on soil properties and vegetation type were also assembled. Considering data from Prenart tension collectors, which were used at nearly all the sites, mean annual concentrations ranged from 1.3 to 97.5 g m(-3) with means of 19.5 (standard deviation 15.2) and 27.6 (SD 23.3) g m(-3) for moorland and forest sites respectively. Interannual mean DOC concentration at an individual site varied by only 1.5-fold, averaged over all sites with at least three years' data. Concentrations during summer months (April to September) were on average 17% greater than those in winter (October to March). If data from two sites (the single peatland and an unusual forest site) were ignored, DOC concentrations were strongly inversely related to water flux, estimated from rainfall and evaporation data. Fluxes of DOC, calculated by combining concentration with water flux, ranged from 2.2 to 71.9 gC m(-2) yr(-1) over all sites and years, with overall means of 19.2 (SD 13.6) and 12.2 (SD 13.9) gC m(-2) yr(-1) for the moorland and forest sites respectively. However, if the two exceptional sites were omitted, the overall mean was 9.1 gC m(-)(2) yr(-1) with a standard deviation of only 4.9 gC m(-2) yr(-1). Annual DOC flux was strongly dependent upon annual water flux, varying by 3.5-fold between years when averaged over all sites. On average, 75.5% of the DOC was exported during the winter period (October to March). | 18,814,901 |
Ultraviolet light and photosensitising agents activate TRPA1 via generation of oxidative stress. | TRPA1, a Ca(2+)-permeable cation channel that is expressed in sensory neurones, is involved in the perception of chemical irritants and mechanical hyperalgesia. TRPA1 is activated by either covalent or reversible binding of various chemical compounds, including allylisothiocyanate or acrolein, and is further sensitised by increases in the intracellular Ca(2+) concentration. We here demonstrate that TRPA1 confers a sensitivity towards near ultraviolet (UVA) light, which rapidly causes Ca(2+) entry. In electrophysiological recordings in whole cell and inside out modes, exposure to UVA light activated typical TRPA1 currents in a wavelength-dependent and membrane-delimited manner. In the presence of the photosensitising agents acridine orange (100 nM) or hypericin (10 nM), the sensitivity of light-induced TRPA1 activation was increased and extended towards the visible spectrum. Since extracellular application of hydrogen peroxide mimicked the effect of UVA irradiation and since dithiothreitol partly reversed the activation by UVA exposure, we conclude that reactive oxygen species may mediate the light-induced activation of TRPA1. Accordingly, hydrogen peroxide induced a TRPA1 activation with a membrane-delimited mode of action that was attenuated by dithiothreitol. Intracellular but not extracellular application of FeSO(4), which catalyses the formation of highly reactive hydroxyl radicals potentiated the hydrogen peroxide-stimulated TRPA1 activation. We conclude that, via generation of reactive oxygen species, light-induced TRPA1 activation provides an additional mode of activation, which renders TRPA1 a likely molecular candidate in processes leading to painful or burning sensations during photodynamic therapy or upon local application of hydrogen peroxide. | 18,814,910 |
Effect of polymyxin B and environmental conditions on isolation of Brucella species and the vaccine strain RB51. | Brucella are resistant to polymyxin B (PB), but their relative susceptibility to PB and its derivative, colistin (COL) has not been rigorously or systematically studied. Comparative susceptibility of Brucella reference strains, vaccine strain RB51, and Brucella isolates from marine mammals to these two cationic peptides were determined by Etest. Vast differences among Brucella species were found in susceptibility to both PB and COL. Brucella demonstrated similar pattern of relative susceptibility to PB as that of COL, but they were less susceptible to COL. Both B. melitensis and B. suis were the least susceptible to polymyxins and rough strains were more susceptible to both PB and COL than the smooth except for the BvrR mutant. Strains were generally less susceptible to PB when cultured in CO(2) rather than ambient air; some became more susceptible in acidified medium. Results show that environment cultural conditions must be considered when selecting for CO(2)-independent strains of Brucella especially the vaccine strain RB51 on selective media containing PB. Our observations extend basic knowledge of the differential resistance of Brucella to polymyxins. | 18,814,911 |
Reversing opinions on Dollo's Law. | Dollo's Law, the idea that the loss of complex features in evolution is irreversible, is a popular concept in evolutionary biology. Here we review how application of recent phylogenetic methods, genomics and evo-devo approaches is changing our view of Dollo's Law and its underlying mechanisms. Phylogenetic studies have recently demonstrated cases where seemingly complex features such as digits and wings have been reacquired. Meanwhile, large genomics databases and evo-devo studies are showing how the underlying developmental pathways and genetic architecture can be retained after the loss of a character. With dwindling evidence for the law-like nature of Dollo's Law, we anticipate a return to Dollo's original focus on irreversibility of all kinds of changes, not exclusively losses. | 18,814,933 |
Chromosomal instability is a risk factor for poor prognosis of adenocarcinoma of the lung: Fluorescence in situ hybridization analysis of paraffin-embedded tissue from Korean patients. | In this study, we sought to evaluate the prognostic importance of chromosomal instability (CIN) in adenocarcinoma (AC) of the lung. The relationship between CIN detected by fluorescence in situ hybridization (FISH) and survival in AC patients was examined. Sixty-three surgical specimens of lung AC were analyzed. To identify tumors with CIN, p16 and multi-target DNA FISH assays for c-myc, chromosome 6, EGFR, and chromosome 5 (LAVysion, Vysis) were performed on nuclei extracted from paraffin-embedded tumor tissues. Survival rates were compared in terms of sex, age, histology, T factor, N factor, CIN, and smoking status. A sample was classified as CIN-positive if at least three of the five chromosomes were positive. Out of the 63 specimens, 32 (39.7%) were CIN-positive. The 5-year overall disease-free survival rate was 58.7% as a whole, 46.9% for CIN-positive patients and 71.0% for the CIN-negative patients [hazard ratio (HR), 2.34; 95% confidence interval (CI), 1.04-5.26; p = 0.04]. The 5-year overall survival rate was 81.0%, 68.7% for CIN-positive patients and 93.5% for the CIN-negative patients (HR, 5.64; 95% CI, 1.23-25.70; p = 0.026). In multivariate analysis after adjusting for pathologic nodal staging, tumor staging, sex, age, and smoking history, compared with the CIN-negative patients, the CIN-positive status remained significantly associated with decreased overall survival (HR, 8.48; 95% CI, 1.66-43.42; p = 0.010). CIN can be effectively detected in primary AC of lung using FISH analysis. CIN is associated with poor prognosis for AC, and may thus be utilized as an independent prognostic factor for the disease. | 18,814,932 |
Antinociceptive effect of resveratrol in carrageenan-evoked hyperalgesia in rats: prolonged effect related to COX-2 expression impairment. | Resveratrol is a natural polyphenol that protects from cancer and cardiovascular diseases. Resveratrol is able to induce apoptotic cell death and it inhibits the cyclooxygenase (COX) cascade. We measured the antinociceptive effect of resveratrol on carrageenan-induced hyperalgesia, prostaglandin-E2 (PGE2) concentration in CSF and COX-1/COX-2 gene expression in the spinal cord and dorsal root ganglion (DRG) in rats. Resveratrol induced a prolonged antinociceptive effect, which was correlated to the inhibition of COX-2 mRNA increase in DRG and cord elicited by carrageenan. An increase in the basal threshold of mechanical nociception was also observed with resveratrol in the absence of any inflammatory insult. A rapid bilateralisation of COX-2 mRNA production, not accompanied by a parallel increase in c-Fos expression, was observed in spinal cord three hours after the inflammatory insult. This increase in COX-2 mRNA concentration in the spinal cord on the opposite side of the inflammatory insult was abolished by resveratrol. In conclusion, the antinociceptive effect exhibited by resveratrol was related to the prevention of COX-2 mRNA increase induced by carrageenan. Resveratrol also prevented the bilateralisation of COX-2 expression. The later effect, together with the prolonged analgesia induced by a single injection, may be of great benefit for preventing chronic pain states often seen after inflammatory insults. | 18,814,970 |
Reduced Sertoli cell number and altered pituitary responsiveness in male lambs undernourished in utero. | The nutritional status of females during pregnancy can have profound effects on the fetus reproductive system development that could affect the reproductive potential as later as in adulthood (fetal programming). The aim of the present study was to examine the effects of maternal nutrient restriction imposed during different periods of gestation on pituitary responsiveness at different ages postnatal and on Sertoli cell number in male offspring. Pregnant ewes were fed to 100% of Metabolizable Energy and Crude Protein requirements throughout pregnancy (Control) or to 50% from 0 to 30 (R1) or from 31 to 100 days of gestation (R2). Male lambs were selected and fed to appetite throughout the study. At 2, 5.5 and 10 months of age a GnRH challenge was conducted. At slaughter (10 months) testes were removed and examined histologically. Maternal undernutrition did not affect the time of the onset of puberty, defined as the first increase in plasma testosterone concentrations > or =1 ng/ml. The LH and FSH response to GnRH challenge did not differ between groups at 2 and 5.5 months but at 10 months of age a higher (P<0.05) FSH response was found in R2 group. Testes weight did not differ between groups at slaughter. Mean Sertoli cell number was significantly lower in animals of R2 group compared with Control (P<0.01). A smaller seminiferous tubules diameter was detected in R2 group (P<0.05), while the diameter of the lumen was similar in all groups. Collectively, these results provide clear evidence for a direct effect of nutrient restriction during pregnancy on Sertoli cell number in adulthood. The lower number of Sertoli cells is the most candidate factor for the higher pituitary activity through a reduction in the suppressive effect of inhibin. | 18,814,977 |
A simple and rapid high-performance liquid chromatographic method for the determination of bisoprolol fumarate and hydrochlorothiazide in a tablet dosage form. | A simple and precise high performance liquid chromatographic method has been developed and validated for the simultaneous determination of bisoprolol fumarate (BF), and hydrochlorothiazide (HCTZ) in a tablet formulation. Chromatography was carried out at 25 degrees C on a 4.6 mm x 250 mm, 5 microm cyano column with the isocratic mobile phase of 0.1M aqueous phosphate buffer, acetonitrile and tetrahydrofuran (85:10:5, v/v/v) at a flow rate of 1.0 ml/min. The UV detection was carried out at 225 nm. HCTZ and BF were separated in less than 10 min with good resolution and minimal tailing, without interference of excipients. The method was validated according to ICH guidelines and the acceptance criteria for accuracy, precision, linearity, specificity and system suitability were met in all cases. The method was linear in the range of 50-150 microg/ml for BF and 125-375 microg/ml for HCTZ. | 18,814,989 |
Anion gap as a screening tool for elevated lactate in patients with an increased risk of developing sepsis in the Emergency Department. | Serum lactate levels are a useful tool in monitoring critically ill patients, especially those who are septic. However, lactate levels are often not routinely drawn or rapidly available in some institutions. The objective of this study was to determine if a readily available anion gap (AG) could be used as a surrogate marker for abnormal lactate level in Emergency Department (ED) patients at risk for sepsis. Prospective, observational cohort study of consecutive ED patients seen at an urban university tertiary care referral center with 46,000 annual ED visits. ED patients aged 18 years or older presenting with clinically suspected infection were eligible for enrollment if a serum chemistry and lactate levels were drawn during the ED visit. During the 9-month study period, 1419 patients were enrolled. The initial basic chemistry panels, calculated AG, and lactate levels drawn in the ED were collected. We defined, a priori, an AG > 12 and a lactate > 4 mmol/L to be abnormal. Analysis was performed with Student's t-test, operating characteristics with 95% confidence intervals, and logistic regression. The mean AG was 11.8 (SD 3.6) and the mean lactate was 2.1 (SD 1.3). For an AG > 12, the mean lactate was 2.9 (SD 1.7), compared with 1.8 (SD 0.8) for an AG < 12. The sensitivity of an elevated AG (> 12) in predicting elevated lactate levels (> 4 mmol/L) was 80% (72-87%) and the specificity was 69% (66-71%). Patients with a gap > 12 had a 7.3-fold (4.6-11.4) increased risk of having a lactate > 4 mmol/L. The area under the curve was 0.84. This study suggests that an elevated AG obtained in the ED is a moderately sensitive and specific means to detect elevated lactate levels in ED patients at risk for sepsis. This information may be somewhat helpful to Emergency Physicians to risk-stratify their patients to provide more aggressive early resuscitation. | 18,815,002 |
Willow bark extract (Salicis cortex) for gonarthrosis and coxarthrosis--results of a cohort study with a control group. | The examination of the effectiveness and tolerance of willow bark extract in patients with gonarthrosis and coxarthrosis compared to conventional therapies. In an open, multicentric observational study with reference treatment, 90 patients were treated with a standardised willow bark extract preparation, 41 patients with a standard therapy prescribed by a doctor and 8 patients with a combination of the two. After 3 and finally 6 weeks the effectiveness and tolerance were determined by the doctor (clinical findings, recording of adverse events, global tolerance) and by the patients (WOMAC questions concerning pain and stiffness, questions on general state of health). A total of 88 patients in the willow bark group and 40 patients in the reference group completed the study. The doctors and patients judged the effectiveness in both groups to be comparable. After 6 weeks the effectiveness of the willow bark extract tended to be assessed as better than in the group undergoing conventional therapy. Also in the subgroup of chronically sick patients (>3 months), after 6 weeks the effectiveness of both forms of treatment was comparable; however, the effect was slower to set in the willow bark group than in the reference group. Doctors and patients assessed the tolerance of the willow bark extract to be better than the conventional therapy. Adverse effects of the drugs did not occur in the willow bark group; one case each of reflux symptoms occurred in the reference group and the For treating mild or fairly severe cases of gonarthrosis and coxarthrosis the effect of willow bark extract is comparable to that of standard therapies, without the corresponding side effects having to be accepted. | 18,815,018 |
Achieving asthma control in practice: understanding the reasons for poor control. | Achieving asthma control remains an elusive goal for the majority of patients worldwide. Ensuring a correct diagnosis of asthma is the first step in assessing poor symptom control; this requires returning to the basics of history taking and physical examination, in conjunction with lung function measurement when appropriate. A number of factors may contribute to sub-optimal asthma control. Concomitant rhinitis, a common co-pathology and contributor to poor control, can often be identified by asking a simple question. Smoking too has been identified as a cause of poor asthma control. Practical barriers such as poor inhaler technique must be addressed. An appreciation of patients' views and concerns about maintenance asthma therapy can help guide discussion to address perceptual barriers to taking maintenance therapy (doubts about personal necessity and concerns about potential adverse effects). Further study into, and a greater consideration of, factors and patient characteristics that could predict individual responses to asthma therapies are needed. Finally, more clinical trials that enrol patient populations reflecting the real world diversity of patients seen in clinical practice, including wide age ranges, presence of comorbidities, current smoking, and differing ethnic origins, will contribute to better individual patient management. | 18,815,019 |
Imidazoles: SAR and development of a potent class of cyclin-dependent kinase inhibitors. | An imidazole series of cyclin-dependent kinase (CDK) inhibitors has been developed. Protein inhibitor structure determination has provided an understanding of the emerging structure activity trends for the imidazole series. The introduction of a methyl sulfone at the aniline terminus led to a more orally bioavailable CDK inhibitor that was progressed into clinical development. | 18,815,031 |
Needle in the haystack: structure-based toxin discovery. | In the current data-rich era, making the leap from sequence data to knowledge is a task that requires an elegant bioinformatics toolset to pinpoint pressing research questions. Therefore, a strategy to expand important protein-family knowledge is required, particularly in cases in which primary sequence identity is low but structural conservation is high. For example, the mono-ADP-ribosylating toxins fit these criteria and several approaches have been used to accelerate the discovery of new family members. The strategy evolved from conduction of PSI-BLAST searches through to the combination of secondary-structure prediction with pattern-based searches. However, a newly developed tactic, in which fold recognition dominates, reduces reliance on sequence similarity and advances scientists toward a true structure-based protein-family expansion methodology. | 18,815,047 |
Synthesis and biological evaluation of immunosuppressive agent DZ2002 and its stereoisomers. | DZ2002 and its related stereoisomers were efficiently synthesized. The optical data of (R)- and (S)-DZ2002 were disclosed here for the first time. Their inhibitory potency was evaluated on SAHase and MLR assay in the mean time. In accordance with respective inhibitory potency of SAHase, the immunosuppressive potency order was demonstrated as (S)-DZ2002>(Rac)-DZ2002>(R)-DZ2002>(Keto)-DZ2002. These results indicate (S)-configuration of 2-chiral center in DZ2002 is important for binding with SAHase. | 18,815,049 |
Solid state water motions revealed by deuterium relaxation in 2H2O-synthesized kanemite and 2H2O-hydrated Na+-zeolite A. | Deuterium NMR relaxation experiments, low temperature deuterium NMR lineshape analysis, and FTIR spectra are consistent with a new model for solid state jump dynamics of water in (2)H(2)O-synthesized kanemite and (2)H(2)O-hydrated Na(+)-Zeolite A. Exchange occurs between two populations of water: one in which water molecules are directly coordinated to sodium ions and experience C(2) symmetry jumps of their OH bonds, and a population of interstitial water molecules outside the sodium ion coordination sphere that experience tetrahedral jumps of their OH bonds. For both samples the C(2) jump rate is much faster than the tetrahedral jump rate. (2)H NMR relaxation experiments match well with the fast exchange regime of the model over a wide range of temperatures, including room temperature and above. For hydrated Zeolite A, the kinetic activation parameters for the tetrahedral and C(2) symmetry jumps are Delta H tet++=+17 kJ/mol, Delta S tet++=-109 J/(mol K), Delta H C2++=+19 kJ/mol, and Delta S C2++=-20 J/(mol K). For kanemite, Delta H tet++ =+23 kJ/mol, Delta S tet++=-69 J/(mol K), Delta H C2++ =+23 kJ/mol, and Delta S C2++ =-11 J/(mol K). | 18,815,060 |
A case of Staphylococcus saccharolyticus pneumonia. | This paper reports a case of a very rare and dangerous disease, Staphylococcus saccharolyticus pneumonia. In this tragic case, a 21-year-old patient died after he did not receive timely diagnosis and proper treatment. | 18,815,064 |
Development and validation of a LC/MS/MS method for quantifying the next generation calcineurin inhibitor, voclosporin, in human whole blood. | A rapid, accurate, and reproducible liquid chromatography electrospray tandem mass spectrometry (LC/ESI-MS/MS) method was developed and validated for the therapeutic drug monitoring of voclosporin in human whole blood. Sample aliquots of 100muL were processed utilizing a protein precipitation procedure that contained a mixture of methanol, 0.2M ZnSO(4), and deuterated voclosporin internal standard. Supernatant was injected onto a Zorbax SB-C8, 2.1x12.5mm column (at 60 degrees C), and washed with water-acetonitrile, supplemented with 0.02% glacial acetic acid and 0.02mM sodium acetate, to remove poorly retained components. After washing, water-MeOH (with 0.02% glacial acetic acid and 0.02mM sodium acetate) was used to elute the voclosporin and internal standard to the Applied Biosystems/MDS-Sciex API3000 mass spectrometer for detection in multiple reaction monitoring. Analytical performance was assessed in the range of 1-200ng/ml in whole blood. This method has been used to quantify concentrations of voclosporin in whole blood from healthy volunteers participating in a pharmacokinetic study. | 18,815,080 |
A 4-channel coil array interconnection by analog direct modulation optical link for 1.5-T MRI. | Optical glass fiber shows great advantages over coaxial cables in terms of electromagnetic interference, thus, it should be considered a potential alternative for magnetic resonance imaging (MRI) receive coil interconnection, especially for a large number coil array at high field. In this paper, we propose a 4-channel analog direct modulation optical link for a 1.5-T MRI coil array interconnection. First, a general direct modulated optical link is compared to an external modulated optical link. And then the link performances of the proposed direct modulated optical link, including power gain, frequency response, and dynamic range, are analyzed and measured. Phantom and in vivo head images obtained using this optical link are demonstrated for comparison with those obtained by cable connections. The signal-to-noise (SNR) analysis shows that the optical link achieves 6%-8% SNR a improvement over coaxial cables by elimination of electrical interference between cables during MR signal transmission. | 18,815,095 |
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