title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Isolated posterior cruciate ligament injuries associated with closed tibial shaft fractures: a report of two cases. | Knee ligament injuries associated with tibia shaft fractures are usually neglected and treatment is delayed. To our knowledge, no case presentation discusses the clinical result of closed tibial shaft fracture with concomitant ipsilateral isolated PCL injury. In this literature, we report the clinical result of two cases that sustained closed tibial shaft fracture with concomitant PCL injury and discuss the treatment options. We report the clinical result of two cases that sustained closed tibial shaft fracture with concomitant posterior cruciate ligament (PCL) injury. Case 1 received open reduction with plate fixation for the tibial shaft fracture, and he also received arthroscopic reconstruction of PCL with bone-patellar tendon-bone graft due to neglecting PCL injury 5 months later after fracture fixation. Case 2 sustained left tibial-fibular shaft fracture with isolated PCL injury confirmed by magnetic resonance image on the first day of injury. She received tibia fixation with intramedullary nail and conservative treatment with bracing and rehabilitation for PCL injury. In case 1, the male patient only focused on fracture healing without any knee rehabilitation. His knee flexed deeply for protected weight bearing in the injured leg which may have exacerbated the posterior instability and reduced the possibility of PCL healing. The end result of knee function was poor even though PCL reconstruction was done later. In case 2, the female patient with diagnosed posterior cruciate ligament injury on the day of injury, her knee was immobilized in brace with full extension, which improved PCL healing. In addition, she received rehabilitation of quadriceps strengthening, and hamstring muscle contraction was avoided in her daily activity. After rehabilitation, the female patient did not complain of severe subjective instability even with an obvious posterior translation on posterior drawer test. We need to perform a careful physical examination of ipsilateral knee in cases of leg fractures, and MRI of knee before surgery if any doubt exists. However, a further research is needed to conclude on the best operation and rehabilitation program in patients with combined tibial shaft fracture and PCL injury. | 18,758,794 |
Expression of matrix metalloproteinases and their inhibitors in cords and nodules of patients with Dupuytren's disease. | Dupuytren's disease is a fibroproliferative disorder characterized by thickening of the palmar fascia. Several studies indicate that MMPs and TIMPs may play a key role in the onset or progression of Dupuytren's disease and related disorders. In this study, we used a quantitative reverse-transcription PCR methodology to profile the expression of TIMP1, TIMP2, MMP2, and MMP9 in nodule and cord tissue from patients with Dupuytren's disease and compared this with normal palmar fascia taken at carpal tunnel release. Tissue from patients with Dupuytren's disease was taken at fasciectomy (n = 30; 23 men and 7 women; average age 61.3 +/- 9.5 years). Samples were divided into regions of nodule and cord according to gross morphology. Normal fascia was taken from patients without Dupuytren's contracture who had carpal tunnel release (n = 30; 14 men and 16 women; average age 63 +/- 11 years). Expression of mRNA was calculated using a relative quantification method (Pfaffl). Statistical analysis was performed using the Mann-Whitney test. The level of significance was considered to be P < 0.05. In comparison to normal fascia, the cords and nodules from patients with Dupuytren's disease showed significant upregulation for TIMP1 and TIMP2 (P < 0.05). The expression of TIMP1 was significantly higher in nodules in comparison to cord tissue (P < 0.05). The expression of MMP2 was significantly upregulated in tissue of patients with Dupuytren's contracture in comparison to normal tissue (P < 0.05). The expression of MMP2 was significantly higher in nodules in comparison to cord tissue (P < 0.05). There was no significant difference in the relative expression of MMP9 in nodules and cord tissue of patients with Dupuytren's contracture in comparison to normal fascia from patients with carpal tunnel syndrome. The balance between MMPs and their natural inhibitors is disturbed in patients with Dupuytren's disease. The decrease in MMP-to-TIMP expression can cause increased synthesis and deposition of collagen, leading to palmar fibromatosis. The high expression of MMP2 may represent an unsuccessful attempt to reduce collagen deposition. In the future, a treatment that downregulates TIMPs but increases the activity of MMPs may be an appropriate therapy for Dupuytren's disease. | 18,758,795 |
MRI appearances of acute idiopathic scrotal oedema in an adult. | Acute idiopathic scrotal oedema is an uncommon cause of acute painless scrotal swelling that is usually seen in children. Traditionally, ultrasound has been used to help establish the diagnosis in the appropriate clinical setting. We report the MRI appearances of acute idiopathic scrotal oedema in a 51-year-old male with associated involvement of the penis. | 18,758,833 |
Bacterial succession within an ephemeral hypereutrophic Mojave Desert playa Lake. | Ephemerally wet playas are conspicuous features of arid landscapes worldwide; however, they have not been well studied as habitats for microorganisms. We tracked the geochemistry and microbial community in Silver Lake playa, California, over one flooding/desiccation cycle following the unusually wet winter of 2004-2005. Over the course of the study, total dissolved solids increased by approximately 10-fold and pH increased by nearly one unit. As the lake contracted and temperatures increased over the summer, a moderately dense planktonic population of approximately 1x10(6) cells ml(-1) of culturable heterotrophs was replaced by a dense population of more than 1x10(9) cells ml(-1), which appears to be the highest concentration of culturable planktonic heterotrophs reported in any natural aquatic ecosystem. This correlated with a dramatic depletion of nitrate as well as changes in the microbial community, as assessed by small subunit ribosomal RNA gene sequencing of bacterial isolates and uncultivated clones. Isolates from the early-phase flooded playa were primarily Actinobacteria, Firmicutes, and Bacteroidetes, yet clone libraries were dominated by Betaproteobacteria and yet uncultivated Actinobacteria. Isolates from the late-flooded phase ecosystem were predominantly Proteobacteria, particularly alkalitolerant isolates of Rhodobaca, Porphyrobacter, Hydrogenophaga, Alishwenella, and relatives of Thauera; however, clone libraries were composed almost entirely of Synechococcus (Cyanobacteria). A sample taken after the playa surface was completely desiccated contained diverse culturable Actinobacteria typically isolated from soils. In total, 205 isolates and 166 clones represented 82 and 44 species-level groups, respectively, including a wide diversity of Proteobacteria, Bacteroidetes, Actinobacteria, Firmicutes, Gemmatimonadetes, Acidobacteria, and Cyanobacteria. | 18,758,846 |
HA/GSA-Rmax ratio as a predictor of postoperative liver failure. | Postoperative mortality after hepatectomy remains high compared with other types of surgery in patients who have cirrhosis or chronic hepatitis. Although there are several useful perioperative markers of liver dysfunction, there are no standard markers for predicting postoperative liver failure. This study investigated risk factors for postoperative liver failure after resection of hepatocellular carcinoma to detect markers that could identify candidates for hepatectomy. Perioperative risk factors for liver failure after hepatectomy were analyzed in 191 patients with hepatocellular carcinoma. Multivariate logistic regression analysis was done to investigate factors with a significant independent influence among 35 variables. The ratio of serum hyaluronic acid to the maximum removal rate of technetium-99 m diethylenetriaminepentaacetic acid galactosyl human serum albumin (hyaluronate/GSA-Rmax ratio) was calculated. Liver failure occurred postoperatively in 16 patients, 3 of whom died. The hyaluronate/GSA-Rmax ratio was a risk factor for postoperative liver failure by univariate analysis and was the only risk factor according to multivariate analysis. All three patients who died had a hyaluronic acid/GSA-Rmax ratio > or = 500 mg min/dl. This ratio had a sensitivity of 88% and a specificity of 92% for predicting liver failure. To reduce postoperative liver failure, preoperative planning should employ various measures of the hepatic functional reserve, including tests of both parenchymal and nonparenchymal liver function. The hyaluronate/GSA-Rmax ratio can predict liver failure after hepatectomy, and a ratio > or = 500 mg min/dl is a relative contraindication to liver resection. | 18,758,848 |
Prognosis of Japanese breast cancer based on hormone receptor and HER2 expression determined by immunohistochemical staining. | We classified Japanese breast cancer patients based on estrogen receptor (ER), progesterone receptor (PR), and HER2 protein expression and compared their prognoses. We compared the background and prognostic factors of 600 patients with breast cancer who were assigned to the following groups: luminal A (ER + and/or PR + and HER2-; n = 431; 71.8%), luminal B (ER + and/or PR + and HER2 + ; n = 27; 4.5%), HER2 (ER-, PR-, and HER2 + ; n = 39; 6.5%) and basal-like (BBC; ER-, PR-, and HER2-; n = 103; 17.2%). Background factors did not significantly differ among the groups. Disease-free survival rates were significantly lower for the luminal B, HER2, and BBC subtypes than for the luminal A subtype. Cancer tended to recur earlier and overall survival was significantly lower for the BBC than for the luminal A and HER2 subtypes. Overall survival rates for the luminal B, HER2, and luminal A subtypes were comparable. The subtype distribution for Japanese and Caucasian patients was comparable. The prognosis for the BBC subtype was poorest among all subtypes. Breast cancer tended to recur earlier for the luminal B and HER2 subtypes than for the luminal A subtype; however, overall survival did not significantly differ among them. | 18,758,851 |
Comparison between open and laparoscopic repair of perforated peptic ulcer disease. | The place of laparoscopic repair of perforated peptic ulcer followed by peritoneal toilet has been established, although it is not routinely practiced. This prospective study compared laparoscopic and open repair of perforated peptic ulcer disease. We evaluated whether the early results from laparoscopic repair resulted in improved patient outcome compared with conventional open repair. All patients who underwent repair of perforated peptic ulcer disease during a 12-month period in our unit were included in the study. The primary end points that were evaluated were total operative time, nasogastric tube utilisation, intravenous fluid requirement, total time of urinary catheter and abdominal drainage usage, time taken to return to normal diet, intravenous/intramuscular opiate use, time to full mobilization, and total in-patient hospital stay. Thirty-three patients underwent surgical repair of perforated peptic ulcer disease (19 laparoscopic repairs and 14 open repairs; mean age, 54.2 (range, 32-82) years). There was no increase in total operative time in patients who had undergone laparoscopic repair (mean: 61 minutes laparoscopic versus 57 minutes open). There was significantly less requirement for intravenous/intramuscular opiate analgesia in patients who had undergone laparoscopic repair (mean time to oral analgesia: 1.2 days laparoscopic versus 3.8 days open). In addition there was a significant decrease in the time that the nasogastric tube (mean: 2.1 days laparoscopic versus 3.1 days open), urinary catheter (mean: 2.3 days laparoscopic versus 3.7 days open) and abdominal drain (mean: 2.2 days laparoscopic versus 3.8 days open) were required during the postoperative period. Patients who had undergone laparoscopic repair required less intravenous fluids (mean: 1.4 days laparoscopic versus 3.1 days open) and returned to normal diet (mean: 2.3 days laparoscopic versus 4.8 days open) and full mobilization significantly earlier than those who had undergone open repair (mean: 2.3 days laparoscopic versus 3.3 days open). In addition, patients who had undergone laparoscopic repair required a shorter in-patient hospital stay (mean: 3.1 days laparoscopic versus 4.3 days open). Laparoscopic repair is a viable and safe surgical option for patients with perforated peptic ulcer disease and should be considered for all patients, providing that the necessary expertise is available. | 18,758,854 |
Lung function response to 12-week treatment with combined inhalation of long-acting beta2 agonist and glucocorticoid according to ADRB2 polymorphism in patients with chronic obstructive pulmonary disease. | Recent reports suggest that beta(2)-adrenergic receptor (ADRB2) genotypes are associated with therapeutic responses to beta(2) agonists in asthmatics. However, few studies have investigated therapeutic responses to beta(2) agonists in chronic obstructive pulmonary disease (COPD) patients. This study investigated immediate bronchodilator response and lung function responses following a 12-week treatment with a long-acting beta(2) agonist combined with a steroid inhaler in patients with COPD with various ADRB2 genotypes. One hundred four patients with chronic obstruction were genotyped for codon 16 and 27 polymorphisms of the ADRB2 gene. The immediate bronchodilator response to beta(2)-agonist treatment was evaluated after inhalation of 400 microg salbutamol. In addition, long-term response was evaluated using observed change in spirometric values before and after the treatment with salmeterol (50 microg) combined with fluticasone propionate (500 microg) inhalation twice daily for 12 weeks. In terms of codon 16 variants, the immediate bronchodilator response to salbutamol was 6.4 +/- 0.8% (% predicted value) in Arg/Arg patients, 4.9 +/- 0.7% in Arg/Gly patients, and 5.8 +/- 1.2% in Gly/Gly patients (p = 0.418). The FEV(1) changes following the 12-week treatment were 7.0 +/- 1.2% in Arg/Arg patients, 3.0 +/- 1.5% in Arg/Gly patients, and 7.2 +/- 1.2% in Gly/Gly patients (p = 0.229). Similarly, there was no difference between codon 27 variants in terms of immediate bronchodilator response or FEV1 changes after 12 weeks of treatment. We were unable to demonstrate an association between ADRB2 genotype and the effect on lung function of 12-week treatment with combined long-acting beta(2) agonist and glucocorticoid inhalation or on the immediate bronchodilator response to a short-acting beta(2) agonist in patients with COPD. | 18,758,858 |
NtbZIP60, an endoplasmic reticulum-localized transcription factor, plays a role in the defense response against bacterial pathogens in Nicotiana tabacum. | A spermine-based signal transduction pathway plays a defensive role against incompatible pathogens. We identified a novel spermine-responsive cDNA from Nicotiana tabacum that encodes a basic region/leucine zipper protein with a putative transmembrane domain. Identity to Arabidopsis thaliana AtbZIP60 was sufficiently high to name the novel cDNA NtbZIP60. Expression analysis revealed that NtbZIP60 is a component of the spermine-signal pathway, and is also involved in the unfolded protein response (UPR), as demonstrated for AtbZIP60. The gene product, NtbZIP60, localizes to the endoplasmic reticulum (ER) in plant cells; once the putative transmembrane domain is eliminated from the intact protein, it targets the nucleus. The putative processed form of NtbZIP60 transactivates target genes through binding to plant-specific UPR cis-elements. Expression of NbbZIP60, an NtbZIP60 ortholog in Nicotiana benthamiana, was significantly up-regulated at 6 h and later time points upon infection with the non-host pathogen Pseudomonas cichorii, while it was unaffected by infection with the compatible pathogen Pseudomonas syringae pv. tabaci. Furthermore, NbbZIP60-silenced N. benthamiana plants allowed higher multiplication of P. cichorii compared to the control plants. Taken together, the results suggest that this ER-localized transcription factor is involved in the spermine-signal transduction pathway and plays an important role in plant innate immunity. | 18,758,894 |
Independent and combined effect of nutrition and exercise on bone mass development. | Food intake provides the necessary components for adequate metabolic functions in bone. Calcium, phosphorus, vitamin D, magnesium, proteins, and fluoride are some of the most important nutrients in this regard. These have different effects on bone mass. Additionally, exercise has been shown to elicit osteogenic responses in bone development; indeed, it seems to potentiate, for example, the effect of calcium supplementation on bone mass. However, the nutrition-exercise-bone mass relationship is complex and needs further in-depth investigation. As a first step, therefore, we reviewed current knowledge about the role of nutrition on the development of bone tissue and how physical activity affects the nutrient-bone relationship. | 18,758,899 |
Cyclic AMP enhances Smad-mediated BMP signaling through PKA-CREB pathway. | We present experimental results indicating involvement of cyclic AMP (cAMP)-mediated signaling in bone morphogenetic protein (BMP)-induced osteoblastic gene expression at the transcriptional level by luciferase activity assay in C2C12 cells using the promoter sequence of the Id1 gene, an early-response gene to BMPs, which contains both a BMP-responsive element (BRE) and a cAMP-response element (CRE). In cells transfected with luciferase gene driven by wild-type Id1 promoter, treatment with BMP-4 increased luciferase expression, which was further enhanced by the addition of dibutyryl cAMP (dbcAMP). This dbcAMP-enhanced luciferase expression was significantly suppressed when the CRE site in the Id1 promoter was replaced by mutated CRE or endogenous CRE-binding protein (CREB) was knocked down by transfection of CREB RNAi. Pretreatment of cells with protein kinase A (PKA) inhibitor, H89, also dramatically reduced dbcAMP-enhanced luciferase expression. Immunoprecipitation assay showed phosphorylated-Smad1/5/8, phosphorylated-CREB, and CREB-binding protein (CBP) formed the transcriptional complex. These data indicate that cAMP-PKA/CREB/CRE signaling potentially enhances BMP-induced transcription through the BRE in the promoter of the BMP-responsive gene through a PKA-mediated pathway. | 18,758,906 |
Matrix vesicles are carriers of bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and noncollagenous matrix proteins. | Matrix vesicles (MVs) are well positioned in the growth plate to serve as a carrier of morphogenetic information to nearby chondrocytes and osteoblasts. Bone morphogenetic proteins (BMPs) carried in MVs could promote differentiation of these skeletal cells. Vascular endothelial growth factor (VEGF) in MVs could stimulate angiogenesis. Therefore, a study was undertaken to confirm the presence of bone morphogenetic protein (BMP)-1 through-7, VEGF, and the noncollagenous matrix proteins, bone sialoprotein (BSP), osteopontin (OPN), osteocalcin (OC), and osteonectin (ON) in isolated rat growth plate MVs. MVs were isolated from collagenase-digested rachitic rat tibial and femoral growth plates. The presence of BMP-1 through BMP-7, VEGF, BSP, ON, OPN, and OC was evaluated by Western blot, plus ELISA analyses for BMP-2 and-4 content. The alkaline phosphatase-raising ability of MV extracts on cultured rat growth plate chondrocytes was measured as a reflection of MV ability to promote chondroosseous differentiation. BMP-1 through-7, VEGF, BSP, ON, OPN, and OC were all detected by Western blot analyses. Chondrocytes treated with MV extracts showed a two-to threefold increase in alkaline phosphatase activity over control, indicating increased differentiation. Significant amounts of BMP-2 and BMP-4 were detected in MVs by ELISA. Combined, these data suggest that MVs could play an important morphogenetic role in growth plate and endochondral bone formation. | 18,758,911 |
Relative efficacies of alpha-tocopherol, N-acetyl-serotonin, and melatonin in reducing non-enzymatic lipid peroxidation of rat testicular microsomes and mitochondria. | In this study, we examined the relative efficacies of alpha-tocopherol, N-acetyl-serotonin, and melatonin in reducing ascorbate-Fe(2+) lipid peroxidation (LPO) of rat testicular microsomes and mitochondria. Special attention was paid to the changes produced on the highly polyunsaturated fatty acids (PUFAs) C20:4 n6 and C22:5 n6. The LPO of testicular microsomes or mitochondria produced a significant decrease of C20:4 n6 and C22:5 n6. Both long-chain PUFAs were protected when the antioxidants were incorporated either in microsomes or mitochondria. By comparison of the IC50 values obtained between alpha-tocopherol and both indolamines, it was observed that alpha-tocopherol was the most efficient antioxidant against the LPO induced by ascorbate-Fe(2+) under experimental conditions in vitro, IC50 values from the inhibition of alpha-tocopherol on the chemiluminescence were higher in microsomes (0.14 mM) than in mitochondria (0.08 mM). The protective effect observed by alpha-tocopherol in rat testis mitochondria was higher compared with microsomes, associated with the higher amount of [C20:4 n6] + [C22:5 n6] in microsomes than that in mitochondria. Melatonin and N-acetyl-serotonin were more effective in inhibiting the LPO in mitochondria than that in microsomes. Thus, a concentration of 1 mM of both indolamines was sufficient to inhibit in approximately 70% of the light emission in mitochondria, whereas a greater dosage of 10 times (10 mM) was necessary to produce the same effect in microsomes. It is proposed that the vulnerability to LPO of rat testicular microsomes and mitochondria in the presence of both indolamines is different because of the different proportion of PUFAs in these organelles. | 18,758,914 |
3D polycaprolactone scaffolds with controlled pore structure using a rapid prototyping system. | Designing a three-dimensional (3-D) ideal scaffold has been one of the main goals in biomaterials and tissue engineering, and various mechanical techniques have been applied to fabricate biomedical scaffolds used for soft and hard tissue regeneration. Scaffolds should be biodegradable and biocompatible, provide temporary support for cell growth to allow cell adhesion, and consist of a defined structure that can be formed into customized shapes by a computer-aided design system. This versatility in preparing scaffolds gives us the opportunity to use rapid prototyping devices to fabricate polymeric scaffolds. In this study, we fabricated polycaprolactone scaffolds with interconnecting pores using a 3-D melt plotting system and compared the plotted scaffolds to those made by salt leaching. Scanning electron microscopy, a laser scanning microscope, micro-computed tomography, and dynamic mechanical analysis were used to characterize the geometry and mechanical properties of the resulting scaffolds and morphology of attached cells. The plotted scaffolds had the obvious advantage that their mechanical properties could be easily manipulated by adjusting the scaffold geometry. In addition, the plotted scaffolds provided more opportunity for cells to expand between the strands of the scaffold compared to the salt-leached scaffold. | 18,758,915 |
The future of implantable defibrillator and cardiac resynchronization therapy trials. | Implantable cardioverter defibrillator (ICD) trials were initially limited to survivors of sudden death. The focus of defibrillator trials in the last decade has been in prophylactic implantation of the device in high risk populations for the prevention of sudden cardiac death. It is the contention in this review that the new focus for implantable defibrillator trials in 2008 and beyond will be on more selective and focused use of this therapy. This could be achieved by selecting ICD patients based on their pathophysiologic and genetic risk. Increasing effort will also be placed on using the device for prevention of spontaneous malignant ventricular tachyarrhythmias and the index clinical sudden death event. Finally, implantable defibrillators will be used in combination in a "hybrid" therapy approach. ICDs will be increasingly combined either with ventricular tachycardia ablation or ventricular fibrillation ablation using catheter techniques. With the addition of cardiac resynchronization therapy in these devices, new clinical trials that use cardiac resynchronization therapy as an early intervention in specific high risk heart failure populations and refinement of the CRT technique to improved optimal results are in progress. Finally, combining ICD devices and regenerative medicine approaches to myocardial replacement therapy are being explored. | 18,758,929 |
Evaluation of insulin and ascorbic acid effects on expression of Bcl-2 family proteins and caspase-3 activity in hippocampus of STZ-induced diabetic rats. | Effects of insulin and ascorbic acid on expression of Bcl-2 family proteins and caspase-3 activity in hippocampus of diabetic rats were evaluated in this study. Diabetes was induced in Wistar male rats by streptozotocin (STZ). Six weeks after verification of diabetes, the animals were treated for 2 weeks with insulin or/and ascorbic acid in separate groups. Hippocampi of rats were removed and evaluation of Bcl-2, Bcl-x(L), and Bax proteins expression in frozen hippocampi tissues were done by SDS-PAGE electrophoresis and blotting. The Bcl-2, Bcl-x(L), and Bax proteins bands were visualized after incubation with specific antibodies using enhanced chemiluminescences method. Caspase-3 activity was determined using the caspase-3/CPP32 Fluorometric Assay Kit. Diabetic rats showed increase in Bax protein expression and decrease in Bcl-2 and Bcl-x(L) proteins expression. The Bax/Bcl-2 and Bax/Bcl-x(L) ratios were found higher compared with non-diabetic control group. Treatments with insulin and/or ascorbic acid were resulted in decrease in Bax protein expression and increase in Bcl-2 and Bcl-x(L) proteins expression. The Bcl-2/Bax and Bcl-x(L)/Bax ratios were found higher in treated groups than untreated diabetic group. Caspase-3 activity level was found higher in diabetic group compared with non-diabetic group. Treatment with insulin and ascorbic acid did downregulated caspase-3 activity. Our data provide supportive evidence to demonstrate the antiapoptotic effects of insulin and ascorbic acid on hippocampus of STZ-induced diabetic rats. | 18,758,938 |
Pulque, an alcoholic drink from rural Mexico, contains phytase. Its in vitro effects on corn tortilla. | Pulque is made by fermenting the agave sap or aguamiel of Agave atrovirens with a whole array of microorganisms present in the environment including several lactic acid bacteria and yeasts such as Saccharomyces cerevisiae. Ascorbic acid was determined in pulque and aguamiel, respectively. Phytase activity in lees, liquid and freeze-dried pulque was assayed by measuring the appearance of phosphate from phytate by a colorimetric method likewise phosphate from phytate present in fresh corn tortilla was measured after in vitro incubation with pulque. Iron, zinc, calcium, magnesium and selenium contents were measured in pulque and corn tortilla as well as in nixtamalized corn flour (NCF), the latter is used to make instant tortilla, since corn provides most of the energy as well as most of the phytate in the Mexican rural diet. Pulque showed phytase activity but much less ascorbic acid and iron than previously reported; additionally, phytase in pulque hydrolyzed most of phytate's corn tortilla. Lees, which is mostly made of pulque's microbiota, significantly accumulated iron and zinc but no selenium. NCF was fortified with iron by the manufacturers but poorly blended. There were significant differences on selenium content between tortillas samples, apparently some soils in central Mexico are selenium deficient. Moderate pulque intake appears to increase the bioavailability of iron and zinc bound by phytate in corn. | 18,758,961 |
Antioxidative and antigenotoxic activity of extracts from cosmos (Cosmos bipinnatus) flowers. | The Cosmos bipinnatus has been used in a traditional herbal remedy for various diseases such as jaundice, intermittent fever, and splenomegaly. The present study describes the preliminary evaluation of antioxidant activities and antigenotoxic effect of Cosmos bipinnatus flowers according to four different colors (white, pink, orange, and violet). The antioxidants properties were evaluated by determining TPC, DPPH RSA, ABTS RSA, and RP. The highest TPC of methanolic CFE (at concentration of 1 mg/ml) showed in violet colored CF (1,013 microM), and IC(50) of DPPH RSA, ABTS RSA, and RP were also the lowest in violet colored CFE with values of 0.61, 1.48, and 0.82 mg/ml, respectively. The antigenotoxic effect of the CFE on DNA damage induced by H(2)O(2) in human leukocytes was evaluated by Comet assay. Pretreatments with CFE produced significant reductions in oxidative DNA damage at the concentration of 500 microg/ml, except for violet colored CFE. The ED(50) value of white colored CFE has shown the highest inhibition (0.40 mg/ml) on H(2)O(2) induced DNA damage, followed by orange > pink > violet color. These results suggested that Cosmos bipinnatus has significant antioxidant activity and protective effect against oxidative DNA damage. | 18,758,962 |
Diagnosis, staging, and surgical treatment of malignant pleural mesothelioma. | The clinical presentation of malignant pleural mesothelioma (MPM) is nonspecific. The process to obtain the correct diagnosis can be challenging and requires a high index of suspicion. Once the diagnosis is made, there is no universally accepted standard of care and treatment decisions are strongly influenced by physician bias. Physicians who see few numbers of patients tend to treat based on symptoms alone by drainage of the pleural effusion and talc pleurodesis, while physicians at several tertiary referral centers tend to take an aggressive multimodality approach incorporating surgical resection, chemotherapy, and radiation. The primary goal of surgery in this setting is the resection of all gross disease. The choice of operation, extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D), depends on disease stage, pulmonary function, philosophy of the treating physician, and type of planned adjuvant therapy. | 18,758,965 |
Utilization of an intron located polyadenlyation site resulted in four novel glutamate decarboxylase transcripts. | Glutamate decarboxylase (GAD) is the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in central nervous system (CNS). Two homologous forms of GAD encoded by separate genes have been identified in mammalian brain, with molecular weight of 65 kDa (GAD65) and 67 kDa (GAD67). In the present study, four novel GAD67 transcripts produced by alternative splicing and polyadenlyation were cloned from rat testis. These novel GAD67 transcripts were widely expressed in non-neuronal tissues. During rat testis maturation, their expression level showed a time dependent change. These transcripts were predicted to synthesis of GAD proteins truncated of the binding site for pyridoxal phosphate, an essential cofactor, therefore cannot function as a decarboxylase. Thus, post-transcriptional processing mechanism as alternative splicing and polyadenlyation may play a crucial role in regulating rat GAD67 gene expression. | 18,758,993 |
Cold adaptation of a mesophilic cellulase, EG III from Trichoderma reesei, by directed evolution. | Cold-active enzymes have received little research attention although they are very useful in industries. Since the structure bases of cold adaptation of enzymes are still unclear, it is also very difficult to obtain cold-adapted enzymes for industrial applications using routine protein engineering methods. In this work, we employed directed evolution method to randomly mutate a mesophilic cellulase, endoglucanase III (EG III) from Trichoderma reesei, and obtained a cold adapted mutant, designated as w-3. DNA sequence analysis indicates that w-3 is a truncated form of native EG III with a deletion of 25 consecutive amino acids at C-terminus. Further examination of enzymatic kinetics and thermal stability shows that mutant w-3 has a higher K(cat) value and becomes Fmore thermolabile than its parent. In addition, activation energies of w-3 and wild type EG III calculated from Arrhenius equation are 13.3 kJ . mol(t-1) and 26.2 kJ . mol(t-1), respectively. Therefore, the increased specific activity of w-3 at lower temperatures could result from increased K(cat) value and decreased activation energy. | 18,759,020 |
Rice bZIP protein, REB, interacts with GCN4 motif in promoter of Waxy gene. | A bifactorial endosperm box (EB), which contains an endosperm motif (EM) and a GCN4 motif, was found in rice Wx promoter. EB was found in 5' upstream region of many seed storage protein genes accounting for these genes expression exclusive in endosperm among various cereals. Many reports demonstrated that the bZIP transcription activators isolated from wheat, barley and maize, etc. regulate the gene expression through binding to the GCN4 motif. In this research, we showed that GCN4 sequence could be recognized by nuclear proteins extracted from immature rice seeds. Furthermore, a rice bZIP protein, REB was isolated by using PCR method and REB fusion protein was expressed in E. coli. The results of gel shift analysis showed that REB could recognize and bind to the GCN4 motif in the Wx gene in addition to binding to the target sequence in the promoter of alpha-globulin. | 18,759,022 |
Genetic mapping of a new semi-dwarf gene, sd-t(t), in indica rice and estimating of the physical distance of the mapping region. | Application and functional study of dwarf and semi-dwarf genes are of great importance to both crop breeding and molecular biology. A new semi-dwarf gene, sd-t(t), non-allelic to sd-1, had been identified in an indica rice variety, Aitaiyin 2. In this study the gene was genetically mapped by using an F(2) population, which consisted of 474 individuals developed from a cross between Aitaiyin 2 and B30. The sd-t(t) gene was located between the RFLP markers R514 and R1408B with a distance of 1.1 cM to R514, and 4.5 cM to R1408B on chromosome 4. A physical contig covering the sd-t(t) mapping region was further constructed by screening a BAC library with R514 and R1408B as probes, and the physical distance between R514 and R1408B was estimated at approximately 147 kb. This result will facilitate map-based cloning of the sd-t(t) gene. | 18,759,026 |
beta-amylase in developing apple fruits: activities, amounts and subcellular localization. | Starch degradation in cells is closely associated with cereal seed germination, photosynthesis in leaves, carbohydrate storage in tuberous roots, and fleshy fruit development. Based on previously reported in vitro assays, beta-amylase is considered one of the key enzymes catalyzing starch breakdown, but up to date its role in starch breakdown in living cells remains unclear because the enzyme was shown often extrachloroplastic in living cells. The present experiment showed that beta-amylase activity was progressively increasing concomitantly with decreasing starch concentrations during apple (Malus domestica Borkh cv. Starkrimson) fruit development. The apparent amount of beta-amylase assessed by Western blotting also increased during the fruit development, which is consistent with the seasonal changes in the enzyme activity. The subcellular-localization studies via immunogold electron-microscopy technique showed that beta-amylase visualized by gold particles was predominantly located in plastids especially at periphery of starch granules, but the gold particles were scarcely found in other subcellular compartments. These data proved for the first time that the enzyme is compartmented in its functional sites in plant living cells. The predominantly plastid-distributed pattern of beta-amylase in cells was shown unchanged throughout the fruit development. The density of gold particles (beta-amylase) in plastids was increasing during the fruit development, which is consistent with the results of Western blotting. So it is considered that beta-amylase is involved in starch hydrolysis in plastids of the fruit cells. | 18,759,031 |
Negative phototropism of rice root and its influencing factors. | Some characteristics of the rice (Oryza sativa L.) root were found in the experiment of unilaterally irradiating the roots which were planted in water: (i) All the seminal roots, adventitious roots and their branched roots bent away from light, and their curvatures ranged from 25 degrees to 60 degrees . The curvature of adventitious root of the higher node was often larger than that of the lower node, and even larger than that of the seminal root, (ii) The negative phototropic bending of the rice root was mainly due to the larger growth increment of root-tip cells of the irradiated side compared with that of the shaded side, (iii) Root cap was the site of light perception. If root cap was shaded while the root was irradiated the root showed no negative phototropism, and the root lost the characteristic of negative phototropism when root cap was divested. Rice root could resume the characteristic of negative phototropism when the new root cap grew up, if the original cells of root cap were well protected while root cap was divested, (iv) The growth increment and curvature of rice root were both influenced by light intensity. Within the range of 0-100 mumol . m(2) -s(-1), the increasing of light intensity resulted in the decreasing of the growth increment and the increasing of the curvature of rice root, (v) The growth increment and the curvature reached the maximum at 30 degrees C with the temperature treatment of 10-40 degrees C. (vi) Blue-violet light could prominently induce the negative phototropism of rice root, while red light had no such effect. (vii) The auxin (IAA) in the solution, as a very prominent influencing factor, inhibited the growth, the negative phototropism and the gravitropism of rice root when the concentration of IAA increased. The response of negative phototropism of rice root disappeared when the concentration of IAA was above 10 mg . L(-1). | 18,759,036 |
Putative cytochrome P450 genes in rice genome (Oryza sativa L. ssp. indica) and their EST evidence. | We discovered 528 putative cytochrome P450s (P450s) in Oryza sativa L. ssp. indica using Arabidopsis thaliana P450s as database. Those putative rice P450s are thought to belong to 40 families classified in Arabidopsis thaliana. We compared distributions of Arabidopsis thaliana and Oryza sativa P450s and found the two species have similar distribution patterns. However, family distributions of two species also have some differences. For example, in rice, the gene number in families of CYP71, CYP72, CYP76, CYP89, CYP94 and CYP709 is more than twice that in Arabidopsis thaliana; and there are 33 CYP705 members in Arabidopsis thaliana but none in rice. We also found gene members in CYP71 and CYP81 are organized as tandem arrays repeated in the rice genome; maybe they are duplications in the evolutionary event. Furthermore, we accumulated expression sequence tag (EST) evidence for 263 putative rice P450s, which are expressed at transcriptional level and more likely to be true P450s. | 18,759,039 |
Up-regulation of micro-RNA-221 (miRNA-221; chr Xp11.3) and caspase-3 accompanies down-regulation of the survivin-1 homolog BIRC1 (NAIP) in glioblastoma multiforme (GBM). | Glioblastoma multiforme (GBM) represents a class of malignant gliomas which rapidly proliferate, invade and destroy surrounding brain tissues. This study examined micro-RNA (miRNA) speciation and miRNA effects on gene expression in six ATCC glioma and GBM cell lines and in 14 glioma and GBM samples obtained from human brain biopsy. We observed selective up-regulation of miRNA-221 and down-regulation of a miRNA-221 messenger RNA target encoding the survivin-1 homolog BIRC1, a neuronal inhibitor of apoptosis protein (NIAP) and marker for neurodegeneration. The expression of BIRC5 (survivin-1) and caspase-3 were found to be significantly up-regulated, particularly in stage IV GBM. These studies suggest that the abundance and speciation of the BIRC family of neural cell fate regulators are differentially regulated in glioma and GBM, and may contribute to progressive changes in apoptotic signaling and altered neural cell cycling functions. | 18,759,060 |
Current and future therapies of pediatric cardiopulmonary arrest. | To review contemporary guidelines and therapies for pediatric cardiac arrest and discuss potential novel therapies. Key articles and guidelines in the field were reviewed along with recent publications in the fields of neurointensive care and neuroscience germane to cerebral resuscitation. A total of 45 articles were reviewed. The majority of arrests in the pediatric population are asphyxial in origin--which differs importantly from the adult population. The International Consensus on CPR guidelines are discussed, including good quality CPR, chest compressions without interruptions, resuscitation with 100% oxygen and subsequent titration of oxygen to normal oxygen saturations, correct dose of epinephrine, and use of hypothermia in the first 12-24 hours. Novel therapies that showed success in animal studies, such as hypertensive reperfusion, thrombolytics, hemodilution and extracorporeal CPR are also discussed. With only 30% return of spontaneous circulation, 12% survival to hospital discharge and 4% intact neurologic survival, pediatric cardiac arrest remains an area of intense research for therapies to improve its outcomes. In addition to the rapid implementation of basic and advanced life support interventions, new therapies that may have value include mild hypothermia, extracorporeal support, promotion of cerebral blood flow and other more novel therapies targeting oxidative stress, excitotoxicity, neuronal death, and rehabilitation. | 18,759,090 |
Morphological variability in selected heterocystous cyanobacterial strains as a response to varied temperature, light intensity and medium composition. | The effect of temperature, light and nutrient composition on morphological traits was determined in seven nostocacean cyanobacteria (Anabaena planctonica, A. sphaerica var. conoidea, A. spiroides, Aphanizomenon gracile, Nostoc sp., Scytonema sp., and Tolypothrix sp.). Their morphological variability was high but only some of the features showed changes reflecting varied growth conditions. The frequency of heterocyst occurrence decreased with increasing nitrogen concentration. Within the range studied, the effect of temperature on heterocyst frequency of Tolypothrix sp. and planktonic Anabaena strains could be fitted by a normal curve with a clear optimum while linear correlation was found in Aphanizomenon gracile. T-and S-type branching was observed in both Scytonema sp. and Tolypothrix sp. strains. T-type branching was found to be markedly dependent on nitrogen concentration. The abundance of necridic cells of Tolypothrix sp. increased linearly with temperature and light intensity. Regularity of trichome coiling of A. spiroides depended on culture medium, suggesting that nutrient composition may be the main controlling factor. In contrast, the effect of the experimental conditions on the dimensions of vegetative cells and heterocysts was weak. Their variability was markedly higher within each experimental treatment than between treatments. | 18,759,118 |
Lack of Na(+),K (+)-ATPase expression in intercalated cells may be compensated by Na(+)-ATPase: a study on MDCK - C11 cells. | The lack of Na(+),K(+)-ATPase expression in intercalated cells (IC) is an intriguing condition due to its fundamental role in cellular homeostasis. In order to better understand this question we compared the activities of Na(+),K(+)-ATPase and Na(+)-ATPase in two MDCK cell clones: the C11, with IC characteristics, and the C7, with principal cells (PC) characteristics. The Na(+),K(+)-ATPase activity found in C11 cells is far lower than in C7 cells and the expression of its beta-subunit is similar in both cells. On the other hand, a subset of C11 without alpha-subunit expression has been found. In C11 cells the Na(+)-ATPase activity is higher than that of the Na(+),K(+)-ATPase, and it is increased by medium alkalinization, suggesting that it could account for the cellular Na(+)-homeostasis. Although further studies are necessary for a better understanding of these findings, the presence of Na(+)-ATPase may explain the adequate survival of cells that lack Na(+),K(+)-ATPase. | 18,759,127 |
Calibration of reference KAP-meters at SSDL and cross calibration of clinical KAP-meters. | In the summer of 2007 the secondary standard dosimetry laboratory (SSDL) in Norway established a calibration service for reference air-kerma product meter (KAP-meter). The air-kerma area product, P(KA), is a dosimetric quantity that can be directly related to the patient dose and used for risk assessment associated with different x-ray examinations. The calibration of reference KAP-meters at the SSDL gives important information on parameters influencing the calibration factor for different types of KAP-meters. The use of reference KAP-meters calibrated at the SSDL is an easy and reliable way to calibrate or verify the P(KA) indicated by the x-ray equipment out in the clinics. Twelve KAP-meters were calibrated at the SSDL by use of the substitution method at five diagnostic radiation qualities (RQRs). The calibration factors varied from 0.94 to 1.18. The energy response of the individual KAP-meters varied by a total of 20% between the different RQRs and the typical chamber transmission factors ranged from 0.78 to 0.91. It is important to use a calibrated reference KAP-meter and a harmonised calibration method in the P(KA) calibration in hospitals. The obtained uncertainty in the P(KA) readings is comparable with other calibration methods if the information in the calibration certificate is correct used, corrections are made and proper positioning of the KAP-chamber is performed. This will ensure a reliable estimate of the patient dose and a proper optimisation of conventional x-ray examinations and interventional procedures. | 18,759,141 |
The scourge: moral implications of natural embryo loss. | It is often claimed that from the moment of conception embryos have the same moral status as adult humans. This claim plays a central role in many arguments against abortion, in vitro fertilization, and stem cell research. In what follows, I show that this claim leads directly to an unexpected and unwelcome conclusion: that natural embryo loss is one of the greatest problems of our time and that we must do almost everything in our power to prevent it. I examine the responses available to those who hold that embryos have full moral status and conclude that they cannot avoid the force of this argument without giving up this key claim. | 18,759,175 |
A critical analysis of the concept and discourse of 'unborn child'. | Despite its prominence in the abortion debate and in public policy, the discourse of 'unborn patient' has not been subjected to critical scrutiny. We provide a critical analysis in three steps. First, we distinguish between the descriptive and normative meanings of 'unborn child.' There is a long history of the descriptive use of 'unborn child.' Second, we argue that the concept of an unborn child has normative content but that this content does not do the work that opponents of abortion want it to do, namely, to establish the independent moral status of fetuses and their rights, the right to life in particular. Third, we argue that the normative content of 'unborn child' should be dependent moral status, not independent moral status. We conclude that the ethical concept of the fetus as a patient should replace the discourse of "unborn child" when that phrase is used normatively. | 18,759,183 |
[Gastroenterology - accusations and errors in treatment: evaluation of the completed expertise process in internal medicine of the expert committee of North Rhineland for the years 2001 to 2005]. | Since three decades the extrajudical expertise procedures of the Expert Committee and Arbitration Group has served to pacify the doctor-patient relationship. Systematic analyses of accusations and errors provide valuable data that help to avoid treatment errors and liability disputes against physicians. Disease of the gastrointestinal tract were found ex post to be the main diagnosis in 10 % of the patients entering complaints. The most common benign diseases were bile duct diseases (1.5 %), acute appendicitis (1.2 %) and diverticulosis (0.9 %); malignant tumours of the digestive organs were found in 1.8 %. About one-third of the procedures were directed internists; with 25 % the quota of treatment errors was less than the general average of one third. With an overproportional frequency (56 %) diagnosis errors were confirmed for the occurrence of appendicitis. Diagnostic and therapeutic endoscopic examinations were the subject of the claimed erroneous treatment by internists in 34 % of the cases: perforations and postinterventional pancreatitis were frequent reasons for filing a complaint. For the resultant injuries, including 4 fatalities, the internists were found to be liable for damages in a total of 17 % of the cases. | 18,759,199 |
[Summary of the annual meeting of the German society for neurogastroenterology and motility, March 28 - 30, 2008 at Castle Hohenkammer]. | The annual meeting of the German Society for Neurogastroenterology and Motility was held at Castle Hohenkammer from 28th to 30th of March 2008 with C. Pehl (Vilsbiburg) as chairman. The members of the Society study the function of the enteric nervous system, gastrointestinal motility, and functional disturbances of the GI tract. Basic researchers as well as clinical scientists are members of the Society and discussed together their results at this meeting. Results from thirty-six working groups from different European countries, USA, and Egypt were presented at the annual meeting. In addition, Prof. Mark Fox (Switzerland/United Kingdom) gave a review lecture entitled "New technologies to evaluate esophageal function". | 18,759,206 |
[Chances and risks of anti-VEGF therapy]. | Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis. Through regulation of haemodynamics, haematopoesis and the immune system, endocrinology and reparative processes, inhibition of VEGF can cause multiple adverse events. Previous data suggest that--even after intravitreal injection--systemic exposure might occur, thus bearing the risk of manifestation of side effects. Experience with intravenous administration of the antibody bevacizumab (Avastin) pointed to the potential consequences of a pan-VEGF blockade. The change of haemodynamic parameters implies a potential influence on the patient's morbidity. Studies already conducted during the approval process do not provide sufficient statistical power when evaluating whether systemic events significantly differ between the treatment and control groups. Retinal perfusion showed an altered vascular tone (change in vessel diameter) following anti-VEGF treatment. Physiological fenestration of the choroicapillaris is significantly reduced. Possible effects on the local oxygen supply in ischaemic tissue have to be considered. In contrast to destructive treatment modalities (laser, cryo), VEGF inhibitors promise the prompt and efficient response of retinal neovascularisation and the preservation of a better function (visual fields). The maturation of growing vessels (pericytes) and the secondary formation of membranes are limiting factors with regard to the time-point at which anti-VEGF therapy is most effective. A diligent use of the available drugs has to take into account which types of exudative retinopathy are showing no or only very limited response to the treatment. | 18,759,208 |
[Pupillography for the assessment of driver sleepiness]. | Sleepiness behind the wheel is the second most frequent cause of fatal highway accidents when trucks are involved. Spontaneous pupillary oscillations provide objective and quantitative measures of the tonic central nervous activation which is a precondition for higher level mental performance. First experience with this method is now available from Germany and Upper Austria, with the aim to analyse the magnitude of the problem sleepiness behind the wheel. The pupillographic sleepiness test (PST) is a well established method in sleep research/medicine and consists of an 11-minute recording of pupil diameter by infrared video pupillography in the sitting subject, followed by automated data analysis. Parameter of analysis is the pupillary unrest index (PUI) for which a normal value data base is available. Car and truck drivers were examined with the mobile version of the device on a voluntary base during campaigns at German roadhouses and during traffic controls by the police in Upper Austria. All drivers were instructed about the hazards of daytime sleepiness and effective countermeasures. First campaigns at German roadhouses found a percentage of excessive sleepiness values of up to 25%. Of 1180 truck and bus drivers controlled in Upper Austria 22.5% showed excessively sleepy results. The pupillographic sleepiness test assesses daytime sleepiness and its mobile version is appropriate for application during pauses or traffic controls. Objective assessments of driver sleepiness offer important contributions to the prevention of sleepiness-related road-traffic accidents. | 18,759,210 |
[The present place of video-assisted procedures in thyroid surgery]. | Standardized surgical technique, the use of ultrasonic dissection and neuro- monitoring, have reduced morbidity in thyroid surgery, so that aesthetic aspects and endoscopic or minimally-invasive thyroid surgery have become more important for the patients. We report on minimally-invasive and endoscopic procedures with either a cervical or extracervical access. Besides current literature we discuss our own results. The critical evaluation of these procedures shows that the standards of endocrine surgery are not at all times entirely observed. We therefore suggest requirements for endoscopic thyroid resection: The access trauma must be minimal, the aesthetic result must be optimal--without visible scars--and the size of the resected thyroid tissue should be the same as in open surgery. It has to be possible to resect the tissue en bloc. Only if the quality of the endoscopic thyroid resection is ensured aesthetic aspects may begin to play a role. If all these demands are fulfilled, the advantages of endoscopic resections do not only cover aesthetic aspects. The first results show less perioperative pain and a shorter stay in hospital. However, to prove this, further studies are necessary. | 18,759,219 |
Two-dimensional fractal growth properties of the filamentous fungus Cryphonectria parasitica: the effects of hypovirus infection. | Whole-colony two-dimensional fractal growth patterns produced by hypovirus-infected Cryphonectria parasitica (EP155/CHV1-EP713) were measured and compared with those produced by the isogenic virus-free strain (EP155) on solid medium. We have quantified statistically significant differences in the rates of expansion and spatial dynamics of colony growth between the two strains and concluded that fractal dimension is affected by the presence of the hypovirus. Therefore, fractal dimension measurement is an effective quantitative tool for testing the effects of mycovirus infection on fungal growth parameters. | 18,759,224 |
Effect of heavy metals on cultural and morphological growth characteristics of halotolerant Penicillium morphotypes. | Four different morphotypes of halotolerant Penicillium isolated from mangroves and salterns, selected on the basis of their morphological dissimilarities, namely, monoverticillate, biverticillate symmetric, biverticillate asymmetric and terverticillate, were studied for their response to the presence of heavy metals - lead, copper and cadmium salts. Lead was the most easily tolerated of the heavy metals tested, and caused the least variations in cultural and morphological characteristics, while cadmium was the most toxic, causing significant cultural and morphological variations. More striking was the observation that resistance to the heavy metals was highest by the terverticillate Penicillium, decreasing in the biverticillate isolates, the monoverticillate isolate showing the least resistance. | 18,759,233 |
Study of the photochemical properties and conical intersections of [2,2'-bipyridyl]-3-amine-3'-ol. | The two isoelectronic bipyridyl derivatives [2,2'-bipyridyl]-3,3'-diamine and [2,2'-bipyridyl]-3,3'-diol are experimentally known to undergo very different excited-state double-proton-transfer processes, which result in fluorescence quantum yields that differ by four orders of magnitude. In a previous study, these differences were explained from a theoretical point of view, because of topographical features in the potential energy surface and the presence of conical intersections (CIs). Here, we analyze the photochemical properties of a new molecule, [2,2'-bipyridyl]-3-amine-3'-ol [BP(OH)(NH(2))], which is, in fact, a hybrid of the former two. Our density functional theory (DFT), time-dependent DFT (TDDFT), and complete active space self-consistent field (CASSCF) calculations indicate that the double-proton-transfer process in the ground and first singlet pi-->pi* excited state in BP(OH)(NH(2)) presents features that are between those of their "parents". The presence of two CIs and the role they may play in the actual photochemistry of BP(OH)(NH(2)) and other bipyridyl derivatives are also discussed. | 18,759,240 |
A hybrid design: case-parent triads supplemented by control-mother dyads. | Hybrid designs arose from an effort to combine the benefits of family-based and population-based study designs. A recently proposed hybrid approach augments case-parent triads with population-based control-parent triads, genotyping everyone except the control offspring. Including parents of controls substantially improves statistical efficiency for testing and estimating both offspring and maternal genetic relative risk parameters relative to using case-parent triads alone. Moreover, it allows testing of required assumptions. Nevertheless, control fathers can be hard to recruit, whereas control offspring and their mothers may be readily available. Consequently, we propose an alternative hybrid design where offspring-mother pairs, instead of parents, serve as population-based controls. We compare the power of our proposed method with several competitors and show that it performs well in various scenarios, though it is slightly less powerful than the hybrid design that uses control parents. We describe approaches for checking whether population stratification will bias inferences that use controls and whether the mating-symmetry assumption holds. Surprisingly, if mating symmetry is violated, even though mating-type parameters cannot be directly estimated using control-mother dyads alone, and maternal effects cannot be estimated using case-parent triads alone, combining both sources of data allows estimation of all the parameters. This hybrid design can also be used to study environmental influences on disease risk and gene-by-environment interactions. | 18,759,250 |
Clinical course and prognosis of hand and wrist problems in primary care. | To describe the course of a new episode of hand and wrist problems in general practice and to identify predictors that are associated with poor outcome at short-term and long-term followup. Patients consulting their general practitioner with hand or wrist problems (no prior consultation in the preceding 3 months) were sent a questionnaire at baseline and at 3, 6, and 12 months of followup. Potential predictors included sociodemographic variables, characteristics of the symptoms, physical activity, and psychosocial factors. General practitioners recorded information on symptoms, signs, and medical diagnosis. The main outcome measure was insufficient improvement of symptoms using the Symptom Severity Scale at short-term (3 months) and long-term (12 months) followup. Twenty-three percent of patients reported complete recovery after 3 months, increasing to 42% at 1 year after first presentation. Higher probability of poor outcome at 3 months was associated with being female, low pain intensity at baseline, and lower personal control at baseline; at 12 months it was associated with older age, being female, reporting symptoms for >3 months at baseline, low scores on the coping strategy "reducing demands," and a higher score on somatization. Discriminative ability of the models was moderate, with areas under the curve after bootstrapping of 0.60 and 0.69 at 3 and 12 months, respectively. More than half of all patients reported residual symptoms at 1 year. Although poor outcome was difficult to predict, age, sex, duration of symptoms, and psychosocial factors were associated with poor outcome of hand and wrist problems. | 18,759,252 |
A systematic review of instruments measuring foot function, foot pain, and foot-related disability in patients with rheumatoid arthritis. | To compose an inventory of instruments that have been described to measure foot function (i.e., pressure and/or gait parameters), foot pain, and foot-related disability in rheumatoid arthritis (RA), and to investigate the clinimetric quality of these measures. A systematic search was conducted in Medline, CINAHL, EMBase, and Sportdiscus. Standardized criteria, extended with levels of evidence, were applied to assess the quality of the clinimetric studies and the properties (i.e., reliability, validity, and responsiveness) of the described instruments. A variety of measurement instruments were identified. Only 16 instruments have been studied for their measurement properties in RA patients: 7 for assessing foot function, 3 for measuring foot-related disability, and 6 for measuring both foot pain and foot-related disability. Thirteen instruments were rated for reliability, of which 10 were rated positively on different levels of evidence. No positive rating for absolute measurement error was applicable for any of the tests. Internal consistency was reported for 7 instruments; 3 assigned a positive rating. For 2 instruments, Rasch analysis was used to assess the methodologic quality. A positive rating was reported for goodness-of-fit only, not for item calibration. Seven instruments were rated for construct validity, and 3 assigned a positive rating. Only 2 instruments were rated positively for responsiveness. This review offers a basis for choosing the most appropriate instruments for measuring foot function, foot pain, and foot-related disability in RA patients, both for clinical practice and for research. Further research on the quality of these measures is urgently needed. | 18,759,256 |
Rho kinase-dependent CCL20 induced by dynamic compression of human chondrocytes. | Mechanical stimulation of cartilage affects tissue homeostasis and chondrocyte function. The chondrocyte phenotype is dependent on cell shape, which is largely determined by the actin cytoskeleton. Reorganization of the actin cytoskeleton results from Rho GTPase activation. The purpose of this study was to examine the roles of both actin and Rho in mechanotransduction in chondrocytes. We embedded human articular chondrocytes in 2 x 6-mm agarose discs at 5 x 10(6) cells/ml and subjected the discs to unconfined dynamic compression at 0.5 Hz. By comparing samples with and without dynamic compression, we identified Rho activation according to the GTP-bound active RhoA measured in cell lysates. We identified rearrangements in filamentous actin structures using fluorescence-labeled phalloidin and confocal microscopy of fixed samples. We identified altered gene expression using TaqMan quantitative reverse transcription-polymerase chain reaction analysis. We tested for a requirement for Rho signaling by performing the dynamic compression in the presence of Rho kinase inhibitors. RhoA activation occurred within 5-10 minutes of dynamic compression. Rho kinase-dependent actin reorganization occurred within 20 minutes after application of dynamic compression and was apparent as "punctate" F-actin structures that were visible under confocal microscopy. We identified early-phase mechanoresponsive genes (CCL20 and inducible nitric oxide synthase) that were highly up-regulated within 1 hour of dynamic compression in a Rho kinase-dependent and actin-dependent manner. Together, these results are the first demonstration that the Rho-Rho kinase pathway and actin cytoskeletal reorganization are required for changes in the expression of genes involved in human chondrocyte mechanotransduction. | 18,759,278 |
Chronic arthritis aggravates vascular lesions in rabbits with atherosclerosis: a novel model of atherosclerosis associated with chronic inflammation. | To determine whether systemic inflammation induced by chronic antigen-induced arthritis (AIA) accelerates vascular lesions in rabbits with atherosclerosis. Two models of atherosclerosis and chronic AIA were combined. Atherosclerosis was induced by coupling a hyperlipemic diet with an endothelial lesion at the femoral arteries, while chronic AIA was induced by ovalbumin injection. Markers in sera and peripheral blood mononuclear cells (PBMCs) as well as vessels and synovial membranes from the rabbits with the double phenotype (both chronic AIA and atherosclerosis) were compared with those from rabbits with each disease alone. Serum levels of interleukin-6, C-reactive protein, and prostaglandin E(2) increased in rabbits with both chronic AIA and atherosclerosis as compared with healthy animals or animals with either chronic AIA alone or atherosclerosis alone. NF-kappaB binding and CCL2 and cyclooxygenase 2 (COX-2) expression were higher in PBMCs from rabbits with both chronic AIA and atherosclerosis than in PBMCs from healthy rabbits. The intima-media thickness ratio of femoral arteries was equally increased in rabbits with atherosclerosis alone and in rabbits with both chronic AIA and atherosclerosis, but the latter group showed a higher level of macrophage infiltration. Femoral CCL2 and COX-2 expression was increased in rabbits with both chronic AIA and atherosclerosis as compared with rabbits with atherosclerosis alone. In the aortas, vascular lesions were found in 27% of rabbits with atherosclerosis alone and in 60% of rabbits with both chronic AIA and atherosclerosis. Rabbits with both chronic AIA and atherosclerosis exhibited more severe synovitis and higher synovial expression of CCL2 than did rabbits with chronic AIA alone. The onset of chronic AIA in animals with atherosclerosis resulted in the local and systemic up-regulation of mediators of tissue inflammation and plaque instability associated with a higher incidence of aortic lesions. This model could represent a novel approach to the study of inflammation-associated atherosclerosis. | 18,759,289 |
The importance of reporting disease activity states in rheumatoid arthritis clinical trials. | To compare the value of reporting treatment effects in rheumatoid arthritis (RA) as relative change from baseline (e.g., American College of Rheumatology [ACR] responder status) with the value of evaluating absolute disease activity states (e.g., remission). We pooled data from several recent RA clinical trials and evaluated patients who had completed a 1-year treatment period (n = 629). We compared levels of functional impairment and radiographic progression among patients meeting the ACR 50% or 70% improvement criteria (ACR50 and ACR70 responders, respectively) who attained remission of disease, low disease activity, or moderate disease activity after 1 year, as assessed by the Simplified Disease Activity Index and the Disease Activity Score in 28 joints. Within the ACR50 and ACR70 responder groups, functional disability and radiographic progression were lowest in patients who had attained disease remission at 1 year, compared with those who had attained low or moderate disease activity. When patients attained the same disease activity category, physical function and radiographic progression did not differ significantly with different response states. Functional and radiographic outcomes are different in patients depending on the disease activity category they attain, even if the same level of response (change from baseline) is achieved. Among patients who attain the same disease activity category, the degree of response they experience does not seem to matter. Assessing actual disease activity as well as disease activity states should constitute an integral part of clinical trial data reporting. | 18,759,299 |
Mutation analyses in amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula, Japan. | To clarify the genetic background of amyotrophic lateral sclerosis (ALS)/parkinsonism-dementia complex (PDC) of the Kii peninsula, Japan (Kii ALS/PDC), we performed extended mutation analyses of three patients with pathologically diagnosed Kii ALS/PDC. Direct sequencing analyses were performed in 19 genes, including ALS/frontotemporal lobar degeneration (FTLD)-related genes (SOD2, SOD3, ALS2/alsin, SMN1, PGRN, ANG, VEGF, VCP, VAPB, DCTN1, CHMP2B, and TARDBP or TDP-43), tauopathy-related gene (GSK3beta), and parkinsonism-related genes (alpha-synuclein, LRRK2, parkin, DJ-1, PINK1, and ATP13A2). Gene dosage analyses were conducted in screening of MAPT, alpha-synuclein, TDP-43 (or TARDBP), GSK3beta, and parkin. We found no mutation in the 19 genes. We found a homozygous nonsynonymous SNP (ALS2/alsin V368M) shared by all the three patients. Gene dosage was normal in MAPT, alpha-synuclein, TDP-43, GSK3beta, and parkin. The present findings, together with a previous negative study on MAPT and SOD1 mutation, further elucidated the lack of causative mutations in all exons, exon-intron boundaries, or some rearrangements of the reported major causative or susceptible genes related to ALS, FTLD, parkinsonism, synucleinopathy, TDP-43 proteinopathy, and tauopathy. However, the familial aggregation and lack of any environment factors suggest that Kii ALS/PDC is caused by other yet unidentified genetic factors. | 18,759,352 |
Magnetization transfer induced biexponential longitudinal relaxation. | Longitudinal relaxation of brain water (1)H magnetization in mammalian brain in vivo is typically analyzed on a per-voxel basis using a monoexponential model, thereby assigning a single relaxation time constant to all (1)H magnetization within a given voxel. This approach was tested by obtaining inversion recovery (IR) data from gray matter of rats at 64 exponentially spaced recovery times. Using Bayesian probability for model selection, brain water data were best represented by a biexponential function characterized by fast and slow relaxation components. At 4.7T, the amplitude fraction of the rapidly relaxing component is 3.4% +/- 0.7% with a rate constant of 44 +/- 12 s(-1) (mean +/- SD; 174 voxels from four rats). The rate constant of the slow relaxing component is 0.66 +/- 0.04 s(-1). At 11.7T, the corresponding values are 6.9% +/- 0.9%, 19 +/- 5 s(-1), and 0.48 +/- 0.02 s(-1) (151 voxels from four rats). Several putative mechanisms for biexponential relaxation behavior were evaluated, and magnetization transfer (MT) between bulk water protons and nonaqueous protons was determined to be the source of biexponential longitudinal relaxation. MR methods requiring accurate quantification of longitudinal relaxation may need to take this effect explicitly into account. | 18,759,367 |
Hydrolysis of cellulose by amorphous carbon bearing SO3H, COOH, and OH groups. | The hydrolysis of cellulose into saccharides using a range of solid catalysts is investigated for potential application in the environmentally benign saccharification of cellulose. Crystalline pure cellulose is not hydrolyzed by conventional strong solid Brønsted acid catalysts such as niobic acid, H-mordenite, Nafion and Amberlyst-15, whereas amorphous carbon bearing SO 3H, COOH, and OH function as an efficient catalyst for the reaction. The apparent activation energy for the hydrolysis of cellulose into glucose using the carbon catalyst is estimated to be 110 kJ mol (-1), smaller than that for sulfuric acid under optimal conditions (170 kJ mol (-1)). The carbon catalyst can be readily separated from the saccharide solution after reaction for reuse in the reaction without loss of activity. The catalytic performance of the carbon catalyst is attributed to the ability of the material to adsorb beta-1,4 glucan, which does not adsorb to other solid acids. | 18,759,399 |
Oil-in-oil emulsions: a unique tool for the formation of polymer nanoparticles. | Polymer latex particles are nanofunctional materials with widespread applications including electronics, pharmaceuticals, photonics, cosmetics, and coatings. These materials are typically prepared using waterborne heterogeneous systems such as emulsion, miniemulsion, and suspension polymerization. However, all of these processes are limited to water-stable catalysts and monomers mainly polymerizable via radical polymerization. In this Account, we describe a method to overcome this limitation: nonaqueous emulsions can serve as a versatile tool for the synthesis of new types of polymer nanoparticles. To form these emulsions, we first needed to find two nonmiscible nonpolar/polar aprotic organic solvents. We used solvent mixtures of either DMF or acetonitrile in alkanes and carefully designed amphiphilic block and statistical copolymers, such as polyisoprene- b-poly(methyl methacrylate) (PI- b-PMMA), as additives to stabilize these emulsions. Unlike aqueous emulsions, these new emulsion systems allowed the use of water-sensitive monomers and catalysts. Although polyaddition and polycondensation reactions usually lead to a large number of side products and only to oligomers in the aqueous phase, these new conditions resulted in high-molecular-weight, defect-free polymers. Furthermore, conducting nanoparticles were produced by the iron(III)-induced synthesis of poly(ethylenedioxythiophene) (PEDOT) in an emulsion of acetonitrile in cyclohexane. Because metallocenes are sensitive to nitrile and carbonyl groups, the acetonitrile and DMF emulsions were not suitable for carrying out metallocene-catalyzed olefin polymerization. Instead, we developed a second system, which consists of alkanes dispersed in perfluoroalkanes. In this case, we designed a new amphipolar polymeric emulsifier with fluorous and aliphatic side chains to stabilize the emulsions. Such heterogeneous mixtures facilitated the catalytic polymerization of ethylene or propylene to give spherical nanoparticles of high molecular weight polyolefins. These nonaqueous systems also allow for the combination of different polymerization techniques to obtain complex architectures such as core-shell structures. Previously, such structures primarily used vinylic monomers, which greatly limited the number of polymer combinations. We have demonstrated how nonaqueous emulsions allow the use of a broad variety of hydrolyzable monomers and sensitive catalysts to yield polyester, polyurethane, polyamide, conducting polymers, and polyolefin latex particles in one step under ambient reaction conditions. This nonpolar emulsion strategy dramatically increases the chemical palette of polymers that can form nanoparticles via emulsion polymerization. | 18,759,463 |
Measurement of the field dependent electrophoretic mobility of surface modified silica/AOT suspensions. | We have investigated the electrophoretic mobility of silica spheres in a silica/AOT/paraffin ternary system as a function of the applied electric field and observed a large discrepancy with data published on a similar system ( Jin, F. H. ; Davis, H. T. ; Evans, D. F. Int. Conf. Digital Printing Technol. 1998, 206-209 ). We attribute the discrepancy to an artifact in the measurement technique used to obtain that published data. We believe the artifact is caused by high velocity particles being "swept" from the measurement volume, thereby biasing the result toward lower mobilities. Thus, the published measurements appear to indicate a high field plateau in mobility data around 500 kV/m. Our results indicate that the silica/AOT/paraffin solution is reaching dielectric breakdown prior to a conclusive high field plateau being unambiguously measured. At low field the mobility is in general agreement with the prior work ( Jin, F. H. ; Davis, H. T. ; Evans, D. F. Int. Conf. Digital Printing Technol. 1998, 206- 209 ). Any proposed models of apparent charging of particles which utilize the presence of a high field plateau are inappropriate unless the high field plateau is clearly established. Our work indicates that caution is required regarding the measurement of electrophoretic mobility at high electric fields. | 18,759,467 |
Photothermal reshaping of gold nanorods depends on the passivating layers of the nanorod surfaces. | Photothermal reshaping of gold nanorods was triggered by pulsed-laser irradiation. The efficiency of the reshaping was strongly dependent on the surface conditions of the gold nanorods. When the gold nanorods were dispersed in concentrated hexadecyltrimethylammonium bromide (CTAB), the gold nanorods were efficiently transformed into a phi-shape. By comparison when poly(styrene sulfonate), poly(vinylpyrrolidone), poly(ethylene glycol), or phosphatidylcholine layers were used, the CTAB layers were found to be a better thermal insulator that helped to enhance the photothermal reshaping of the gold nanorods. | 18,759,472 |
Efficient potassium-ion-templated synthesis and controlled destruction of [2]rotaxanes based on cascade complexes. | The triptycene-based macrotricyclic host can form pseudorotaxane-like cascade complexes with anthraquinone and its tetra-azide terminally functionalized derivative in the presence of potassium ions, which subsequently resulted in the synthesis of three novel potassium-ion-templated [2]rotaxanes 10-12 in high yields by the "threading followed by stoppering" approach. Since the potassium ions act not only as templates during the stoppering reactions but also as nonslipping chocks to shrink the inner diameter of the wheel cavity, the deslipping behaviors of the [2]rotaxanes with different triazole stoppers by peeling off the potassium ions with 18-crown-6 were further investigated. The results show that rotaxanes 10 and 11 can be destroyed, but under the same conditions the dumbbell and ring components of rotaxane 12 remain interlocked. | 18,759,481 |
Water soluble single-walled carbon nanotubes inhibit stimulated endocytosis in neurons. | We report the use of chemically functionalized water soluble single-walled carbon nanotube (SWNT) graft copolymers to inhibit endocytosis. The graft copolymers were prepared by the functionalization of SWNTs with polyethylene glycol. When added to the culturing medium, these functionalized water soluble SWNTs were able to increase the length of various neuronal processes, neurites, as previously reported. Here we have determined that SWNTs are able to block stimulated membrane endocytosis in neurons, which could then explain the previously noted extended neurite length. | 18,759,491 |
Chemical reactivity and biological activity of diketene. | The alkylating potential of diketene (4-methylene-2-oxetanone), the basic unit of many derivatives of pesticides, chemicals, pharmaceuticals, and dyestuffs, was investigated kinetically. The nucleophile 4-( p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to DNA bases, was used as an alkylation substrate. The alkylation reactions were performed in water/dioxane solvent mixtures. To gain insight into the effect of the hydrolysis of diketene on its alkylating efficiency, alkylation and competing hydrolysis were studied in parallel. Conclusions were drawn as follows: (i) Although diketene, unlike other four-membered ring lactones, is inactive as a carcinogen in experimental animals, it shows an alkylating potential of about 2 orders of magnitude higher than beta-propiolactone or beta-butyrolactone, which are classified as possibly carcinogenic to humans by the IARC. (ii) The reactivity of diketene as an alkylating agent is enthalpy-controlled. (iii) The fact that the hydrolysis reaction of diketene is slightly faster than those of other four-membered ring lactones shows that diketene is more efficient than beta-propiolactone or beta-butyrolactone as an alkylating agent, since the hydrolysis of this species poses less competition to the alkylation reaction. (iv) Diketene undergoes acyl fission in the alkylation reaction, which results in an amide bond in the NBP-diketene adduct. The lability of the amide bond as opposed to the amine bonds formed by beta-propiolactone and beta-butyrolactone could be one of the differential factors responsible for the lack of carcinogenicity of diketene. (v) Ab initio calculations of the energy barriers help to understand the unusual reactivity of diketene. | 18,759,502 |
Relationship between p53 expression and gastric cancers in cardia and antrum. | The mutations in p53 gene and accumulation of p53 protein are the most common genetic events in gastric carcinomas. The present study was conducted to compare the frequency of p53 gene overexpression in a consecutive series of adenocarcinomas arising from the cardia and the antrum. This study also evaluates the associations of this gene expression with demographic and clinicopathologic findings (age, sex, histology, and grade of tumor). Retrospective analysis was performed on 111 patients with gastric cancer who had undergone upper gastrointestinal endoscopies in 5th Azar Medical Center (northeastern, Iran), during 1998-2005. The series comprised of 25 patients with cardia adenocarcinoma and 86 patients with antral adenocarcinoma. p53 alteration (nuclear p53 overexpression) was detected by immunohistochemistry. Nuclear p53 overexpression was found in 14 (56%) out of the 25 and 27 (31.3%) out of the 86 patients with cardia and antral adenocarcinomas, respectively. p53 gene overexpression was significantly more frequent in adenocarcinomas of the cardia than the antrum. There were no differences in the clinicopathologic characteristics of the tumors between p53-positive and p53-negative cases in both types of the cancer. This study shows that p53 alterations correlate well with gastric location, and they are more frequent in adenocarcinoma of the cardia than the antrum. This result reinforce the hypothesis that the cancers of the lower esophagus and upper stomach have distinct epidemiologic, pathogenesis, and molecular characteristics from that observed in cancers of the lower part of the stomach. | 18,759,514 |
Proteomic characterization of primary diffuse large B-cell lymphomas in the central nervous system. | The lack of primary lymphoid tissue within the central nervous system (CNS) confounds our understanding of the pathogenesis of primary CNS lymphomas (PCNSLs). Comparing the protein expression of PCNSLs and sporadic systemic lymphomas (SSLs) provides a useful strategy for identifying a molecular signature that characterizes disease-associated features and provides information regarding tumor initiation and progression. Seven diffuse large B-cell PCNSLs were selected to undergo 2D gel electrophoresis, and profiled proteomes from these PCNSLs were compared with those from 7 diffuse large B-cell SSLs. Distinguishing proteins were sequenced using mass spectrometry. Two-dimensional gel electrophoresis identified an average of 706 proteins from each specimen. Computerized gel analysis and manual reconfirmation revealed a 96% similarity in the proteomes of PCNSLs and SSLs. Comparative analysis identified 9 proteins significantly overexpressed (p < 0.05) and 16 proteins downregulated in PCNSLs. The proteomic findings were further validated using Western blot and immunohistochemical staining. The similarities in proteomic patterns between PCNSLs and SSLs suggest that these tumor types share structural similarities, acquired during differentiation. The ultimate fate of lymphomatous cells (CNS vs systemic) may be related to differentially expressed proteins, which function in homing and host processing. Elucidating the roles of these differentially expressed proteins will prove valuable in understanding the pathogenesis of PCNSL. | 18,759,588 |
Epilepsy surgery and tuberous sclerosis complex: special considerations. | Epilepsy surgery for medically refractory seizures among patients with tuberous sclerosis complex (TSC) is a well-accepted treatment option. Many epilepsy centers around the world have published their experience over the past several years, supporting the idea that the best seizure control is obtained when a single tuber and associated epileptogenic zone is documented and targeted surgically. Recent advances in imaging and physiological techniques that reveal the epileptogenic zone have been used successfully in children with TSC who are being evaluated for surgery. As a result, a number of different surgical strategies have emerged, each reflecting the experience, strengths, and referral biases of the individual treating teams. Experience suggests that some patients with TSC who present with seizures that are difficult to localize and do not meet the classic selection criteria for epilepsy surgery may, nevertheless, benefit from surgery. Tuberectomy alone is often not sufficient for obtaining seizure control. Intracranial electrode recordings performed in a large number of children with TSC undergoing epilepsy surgery have raised new questions about the relationship of the cortical tuber to the epileptogenic zone in TSC. A careful assessment of the risks and benefits of any surgical strategy, compared with those associated with continued refractory epilepsy, should be considered by the treating team in conjunction with the patient's family. Epilepsy surgery has not only benefited many children with TSC, but it also facilitates the understanding of epileptogenesis in TSC. | 18,759,614 |
Phase I trial: safety and feasibility of intracranial electroencephalography using hybrid subdural electrodes containing macro- and microelectrode arrays. | Cerebral cortex electrophysiology is poorly sampled using standard, low spatial resolution clinical intracranial electrodes. Adding microelectrode arrays to the standard clinical macroelectrode arrays increases the spatial resolution and may ultimately improve the clinical utility of intracranial electroencephalography (iEEG). However, the safety of hybrid electrode systems containing standard clinical macroelectrode and microelectrode arrays is not yet known. The authors report on their preliminary experience in 24 patients who underwent implantation of hybrid electrodes. In this study, 24 consecutive patients underwent long-term iEEG monitoring with implanted hybrid depth and subdural grid and strip electrodes; both clinical macroelectrodes and research microelectrodes were used. The patients included 18 women and 6 men with an average age of 35 +/- 12 years (range 21-65). The mean hospital stay was 11 +/- 4 days (range 5-20), with mean duration of implantation 7.0 +/- 3.2 days (range 3-15). Data from the 198 consecutive craniotomies for standard clinical subdural grid insertion (prior to surgery in the 24 patients described here) were used for comparison to investigate the relative risk of complications. Focal seizure identification and subsequent resection was performed in 20 patients. One patient underwent a subsequent operation after neurological deterioration secondary to cerebral swelling and a 5-mm subdural hematoma. There were no infections. The overall complication rate was 4.2% (only 1 patient had a complication), which did not significantly differ from the complication rate previously reported by the authors of 6.6% when standard subdural and depth intracranial electrodes were used. There were no deaths or permanent neurological deficits related to electrode implantation. The authors demonstrate the use of hybrid subdural strip and grid electrodes containing high-density microwire arrays and standard clinical macroelectrodes. Hybrid electrodes provide high spatial resolution electrophysiology of the neocortex that is impossible with standard clinical iEEG. In this initial study in 24 patients, the complication rate is acceptable, and there does not appear to be increased risk associated with the use of hybrid electrodes compared with standard subdural and depth iEEG electrodes. More research is required to show whether hybrid electrode recordings will improve localization of epileptic foci and tracking the generation of neocortical seizures. | 18,759,625 |
Corpus callosotomy in children with intractable epilepsy using frameless stereotactic neuronavigation: 12-year experience at the Hospital for Sick Children in Toronto. | Although corpus callosotomy has been used effectively since the late 1930s to treat severe, medically intractable seizure disorders, particularly atonic or drop-attack seizures, controversy remains as to when, how, and how much surgery should be performed. Intraoperative determination of the extent of callosotomy, the need to stage the procedure, and the side of the interhemispheric approach represent technical issues that remain debatable. The authors report the 12-year experience of the senior author as well as surgical outcomes with corpus callosotomy using a frameless stereotactic neuronavigation system (ISG View Wand and BrainLab). Thirteen consecutive children at The Hospital for Sick Children underwent single-stage corpus callosotomy for medically intractable seizures. The mean age was 10.3 years. Five children underwent partial callosotomy, and 8 underwent complete callosotomy. The side of operative approach to avoid large parasagittal bridging veins was determined by preoperative study of 3D MR imaging/MR venography reconstructed by the neuronavigation system. The extent of callosotomy was determined using intraoperative feedback from the neuronavigation system and postoperative MR imaging. The extent of callosotomy determined by intraoperative neuronavigation and postoperative MR imaging correlated closely in all cases. There were no operative deaths. There was no significant postoperative morbidity related to venous infarction. Four of 5 patients in the partial callosotomy cohort and 7 of 8 patients in the complete callosotomy cohort showed significant improvement in seizure control. The use of frameless stereotactic neuronavigation is a safe, effective, and important surgical adjunct in the planning and execution of successful corpus callosotomy in children with intractable epilepsy. | 18,759,631 |
Recent advances in understanding integrative control of potassium homeostasis. | The potassium homeostatic system is very tightly regulated. Recent studies have shed light on the sensing and molecular mechanisms responsible for this tight control. In addition to classic feedback regulation mediated by a rise in extracellular fluid (ECF) [K(+)], there is evidence for a feedforward mechanism: Dietary K(+) intake is sensed in the gut, and an unidentified gut factor is activated to stimulate renal K(+) excretion. This pathway may explain renal and extrarenal responses to altered K(+) intake that occur independently of changes in ECF [K(+)]. Mechanisms for conserving ECF K(+) during fasting or K(+) deprivation have been described: Kidney NADPH oxidase activation initiates a cascade that provokes the retraction of K(+) channels from the cell membrane, and muscle becomes resistant to insulin stimulation of cellular K(+) uptake. How these mechanisms are triggered by K(+) deprivation remains unclear. Cellular AMP kinase-dependent protein kinase activity provokes the acute transfer of K(+) from the ECF to the ICF, which may be important in exercise or ischemia. These recent advances may shed light on the beneficial effects of a high-K(+) diet for the cardiovascular system. | 18,759,636 |
Characterization of nebulized liposomal amikacin (Arikace) as a function of droplet size. | The stress of nebulization has been shown to alter the properties of liposomal drugs. What has not been demonstrated is whether nebulized liposomes differ as a function of droplet size. Because droplet size influences lung deposition, liposomes with different properties could be deposited in different areas of the lung (e.g., central vs. peripheral). In this report, a liposomal amikacin formulation (Arikace, a registered trademark of Transave, Inc., Monmouth Junction, NJ) that is being developed as an inhaled treatment for gram negative infections was aerosolized with an eFlow (registered trademark of PARI, GmbH, Munich, Germany) nebulizer, reclaimed from the various stages of an Andersen cascade impactor (ACI) and analyzed for lipid-to-drug (L/D) (w/w) ratio, amikacin retention, and liposome size. For the nebulized solution, 99.7% of the total deposited drug was found on ACI stages 0 through 5, which have cutoff diameters of 9, 5.8, 4.7, 3.3, 2.1, and 1.1 microm, respectively. Properties were found to differ for drug reclaimed on stage 0 compared stages 1-5, which were not different from one another. For drug found on stages 1-5 (97% of total drug), the averages (n = 3) for L/D, percent encapsulated amikacin, and liposome mean diameter ranged from 0.59 to 0.68 (w/w), 71% to 75%, 248 to 282 nm, respectively. Drug found on stage 0 (2.8% of total drug) had an average L/D ratio of 0.51 and average liposome mean diameter of 375 nm. Examination of another batch of liposomal amikacin revealed no statistically significant differences between drug reclaimed on stages 0-5. Although a droplet size dependence was noted for one batch of Arikace aerosolized with the eFlow, the effect was considered to be inconsequential because the fraction in doubt represented nonrespirable particles >9 microm and accounted for <3% of the total deposited dose. The methodology applied here appears useful in evaluating aerosolized liposome systems. However, our results should not be assumed to apply to other liposome/drug compositions and nebulizers. | 18,759,656 |
Evaluation of extracellular matrix formation in polycaprolactone and starch-compounded polycaprolactone nanofiber meshes when seeded with bovine articular chondrocytes. | Cartilage defects are a major health problem. Tissue engineering has developed different strategies and several biomaterial morphologies, including natural-based ones, for repairing these defects. We used electrospun polycaprolactone (PCL) and starch-compounded PCL (SPCL) nanofiber meshes to evaluate extracellular matrix (ECM) formation by bovine articular chondrocytes (BACs). The main aim of this work was to evaluate the suitability of PCL and SPCL nanofiber meshes in chondrocyte cultures, and their capability to produce ECM when seeded onto these nanostructured materials. The effect of culture conditions (static vs dynamic) on ECM formation was also assessed. BACs were seeded onto PCL and SPCL nanofiber meshes using a dynamic cell-seeding procedure and cultured under static or dynamic conditions for 4 weeks. Constructs were characterized using scanning electron microscopy, histology, immunolocalization of collagen types I and II, and glycosaminoglycan (GAG) quantification. Results show an extensive cell colonization of the entire nanofiber mesh, for both materials, and that chondrocytes presented typical spherical morphology. Some degree of cell infiltration inside the nanofiber meshes was noticeable for both materials. ECM formation and GAG were detected throughout the materials, evidencing typical construct maturation. PCL and SPCL nanofiber meshes are suitable as supports for ECM formation and therefore are adequate for cartilage tissue-engineering approaches. | 18,759,665 |
Umbilical cord blood stem cells: induction of differentiation into mesenchymal lineages by cell-cell contacts with various mesenchymal cells. | CD133(+) cells isolated from bone marrow, peripheral blood, or umbilical cord blood (UCB) represent an established source of transplantable hematopoietic progenitors. Further, there is increasing evidence that such CD133(+) cell isolates comprise subpopulations capable of differentiating into several mesenchymal lineages. In this study, we investigated conditions under which mesenchymal differentiation can be induced, particularly the role of cell-cell contacts with mesenchymal cells. A purified, nearly homogeneous CD133(+) population of human UCB cells was expanded by stimulation with platelet-derived growth factor and epidermal growth factor, labeled with the fluorescent marker DiI and cocultivated with rat osteoblasts, C2C12 myoblasts, or rat cardiomyocytes, respectively. In control experiments, the two cell types were separated by microporous membranes to avoid cell-cell contacts. Direct coculture of DiI-labeled UCB cells with the different mesenchymal cell populations resulted in both significant morphological changes and upregulation of lineage-specific markers. Expression of osteocalcin, myosin heavy chain, or alpha-actinin confirmed differentiation of the UCB cells into an osteoblastic, myoblastic, or cardiomyocytic phenotype, respectively. In contrast, coculture of UCB cells with the respective inducer cells under conditions preventing cell-cell contacts yielded minor, if any, evidence for such differentiation. Our data, thus, indicate that UCB cell expansion in vitro and subsequent direct cell-cell contacts with mesenchymal cells can induce their differentiation into mesenchymal lineages specific to the cell type they are in contact with. This finding has important implications for understanding the homing of adult stem cells and the promise of UCB as a cell source for tissue engineering and regenerative medicine. | 18,759,667 |
Inkjet-mediated gene transfection into living cells combined with targeted delivery. | In this study a novel method of simultaneous gene transfection and cell delivery based on inkjet printing technology is described. Plasmids encoding green fluorescent protein (GFP) were coprinted with living cells (porcine aortic endothelial [PAE] cells) through the ink cartridge nozzles of modified commercial inkjet printers. Agarose gel electrophoresis analysis showed there was no obvious structural alteration or damage to these plasmids after printing. Transfection efficiency of the printed cells, determined by GFP expression, was over 10%, and posttransfection cell viability was over 90%. We showed that printing conditions, such as plasmid concentration, cartridge model, and plasmid size, influenced gene transfection efficiency. Moreover, genetically modified PAE cells were accurately delivered to target sites within a three-dimensional fibrin gel scaffold and expressed GFP in vitro and in vivo when implanted into mice. These results demonstrate that inkjet printing technology is able to simultaneously transfect genes into cells as well as precisely deliver these cell populations to target sites. This technology may facilitate the development of effective cell-based therapies by combining gene therapy with living cells that can be delivered to target sites. | 18,759,674 |
Reduction in rates of methicillin-resistant Staphylococcus aureus infection after introduction of quarterly linezolid-vancomycin cycling in a surgical intensive care unit. | The burden of infection with antibiotic-resistant gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), continues to increase, leading to substantial morbidity and high mortality rates, particularly in intensive care units (ICUs). Creative interventions may be required to reverse or stabilize this trend. The efficacy of empiric cycling of antibiotics active against gram-positive organisms was tested in a before-after intervention in a single surgical ICU. Four years of baseline data were compared with two years of data compiled after the implementation of a strategy where the empiric antibiotic of choice for the treatment of gram-positive infections (linezolid or vancomycin) was changed every three months. Whatever the initial choice of drug, if possible, the antibiotic was de-escalated after final culture results were obtained. The rates of all gram-positive infections were analyzed, with a particular focus on MRSA and VRE. Concurrently, similar outcomes were followed for patients treated on the same services but outside the ICU, where cycling was not practiced. During the four years prior to cycling, 543 infections with gram-positive organisms were acquired in the ICU (45.3/1,000 patient-days), including 105 caused by MRSA (8.8/1,000 patient days) and 21 by VRE (1.8/1,000 patient-days). In the two years after implementation of cycling, 169 gram-positive infections were documented (28.1/1,000 patient-days; p < 0.0001 vs. non-cycling period), including 11 caused by MRSA (1.8/1,000 patient-days; p < 0.0001 vs. non-cycling period). The percentage of S. aureus infections caused by MRSA declined from 67% to 36%. The rate of infection with VRE was unchanged. Outside the ICU, the yearly numbers of infections with both MRSA and VRE increased over time. Quarterly cycling of linezolid and vancomycin in the ICU is a promising method to reduce infections with MRSA. | 18,759,679 |
Acellular dermal matrix compared with synthetic implant material for repair of ventral hernia in the setting of peri-operative Staphylococcus aureus implant contamination: a rabbit model. | Implant infection is a common clinical complication of abdominal hernia repair. Our objectives were to determine if acellular dermal matrix (ADM) grafts resisted Staphylococcus aureus infection better (as measured by ability to reduce or clear bacterial counts) than synthetic (polytetrafluoroethylene [PTFE]) mesh when used in abdominal wall reconstruction, and to determine whether vascularization of the implant occurred. We hypothesized that the ability of the ADM grafts to vascularize and allow cellular ingrowth would allow the immune system to clear the infection better in these animals. In New Zealand White rabbits (average weight, 3.0 kg), a full-thickness 3 x 3 cm(2) abdominal defect was created, then repaired with an interpositional implant (ADM, n = 62; PTFE, n = 57). Before skin closure, the epidermal surface of each implant was inoculated with 1 mL of S. aureus at various concentrations (10(4) colony-forming units [CFU]/mL, n = 82; 10(6) CFU/mL, n = 27; 10(9) CFU/mL, n = 10), and the rabbits were harvested at either day 7 or day 21. At day 7, ADM grafts inoculated with 10(4) CFU had lower counts or no bacteria (p = 0.006), fewer adhesions (p = 0.005), and fewer abscesses (p = 0.008) than PTFE grafts. By day 21, more ADM (n = 12) than PTFE (n = 0) grafts were free of bacteria (p = 0.002). Fewer rabbits with ADM grafts formed abscesses (13 vs. 19; p = 0.03). When evaluating the 7- and 21-day 10(4) CFU groups combined, a total of 15 rabbits with ADM cleared the bacteria completely vs. none of those with PTFE grafts (p < 0.001). There was no significant difference in bacterial counts or wound complications at days 7 or 21 between PTFE and ADM implants when inoculated with 10(6) CFU. All rabbits inoculated with 10(9) CFU died of sepsis within 48 h. Herniation did not occur in any of the animals. Our study demonstrates that ADM resists surgical site infection caused by S. aureus in an animal model without compromising the ventral hernia repair. This ability of ADM grafts to perform well in the setting of infection is most likely attributable to their capacity to vascularize and aid clearance of bacteria. | 18,759,680 |
Nuclear medicine in the management of thyroid disease. | Thyroid disease management has changed little over the last 60 years and recent work suggests that the older approach remains the most effective. Treatment of benign hyperthyroidism has shown that functional imaging is essentially linked to therapy and uptake of iodine-131 ((131)I) cannot be assumed but should be tested by pre-imaging with radio-isotopes as 10% of patients may not be suitable for (131)I therapy and 1% may have a co-existent cancer. Differentiated thyroid cancer remains unique in that it is almost alone among common solid tumors in that it is routinely cured even if cannot all be removed by surgery. This is achieved in the majority of patients by a treatment introduced in the 1940s and does not involve the use of chemotherapy drugs but a simple and cheap isotope preparation; (131)I. However, in some differentiated thyroid cancers there is no accumulation of (131)I and we know this is due to the loss, or downregulation of the sodium iodide symporter gene. This has led to the development of several strategies to overcome this loss/downregulation, for example with the use of lithium or retinoids or gene treatment. However, all these approaches have yet to be proved in a randomized controlled trial. Advances in imaging especially using (18)F-fluorodeoxy-glucose PET has enabled patients with thyroid cancer to be more accurately imaged, resulting in a greater chance of cure through surgery and external-beam radiotherapy, especially if uptake of (131)I is poor. Another approach has been the idea of using radiolabeled somatostatin analogs, which are able to demonstrate uptake in the tumor and, more recently, beta-emitting isotopes have been used for therapy when other options have failed. Therefore, whilst the treatment of differentiated thyroid cancer is, to some degree, 60 years old, new methods have been proposed and are now being tested in this disease. | 18,759,694 |
Androgen receptor: role and novel therapeutic prospects in prostate cancer. | Androgen receptor (AR) signaling is necessary for the development of prostate cancer. Androgen-deprivation therapy (ADT) for prostate cancer was described over 50 years ago and ADT remains the mainstay of systemic therapy. AR signaling remains intact as the disease evolves to castration-resistant prostate cancer (CRPC). Through cellular adaptations, CRPC continues to rely on androgens and AR growth signaling, and thus AR remains an important therapeutic target. CRPC cells upregulate enzymes used in androgen synthesis, thus providing an intracellular source of androgen despite systemic castration. Compounds in development, such as antiandrogens, lyase inhibitors, heat-shock protein-90 inhibitors, histone deacetylase inhibitors and others, will provide new tools to more effectively reduce ligand, inhibit AR and/or inhibit costimulatory pathways and result in improved clinical outcomes. | 18,759,700 |
Drug-induced serotonin syndrome: a review. | Serotonin syndrome, or serotonin toxicity (ST), is a clinical condition that occurs as a result of an iatrogenic drug-induced increase in intrasynaptic serotonin levels primarily resulting in activation of serotonin(2A) receptors in the central nervous system. The severity of symptoms spans a spectrum of toxicity that correlates with the intrasynaptic serotonin concentration. Although numerous drugs have been implicated in ST, life-threatening cases generally occur only when monoamine oxidase inhibitors are combined with either selective or nonselective serotonin re-uptake inhibitors. The triad of clinical features consists of neuromuscular hyperactivity, autonomic hyperactivity and altered mental status, which may present abruptly and progress rapidly. The awareness of ST is crucial not only in avoiding the unintentional lethal combination of therapeutic drugs but also in recognizing the clinical picture when it occurs so that treatment can be promptly initiated. In this review, the pathophysiology, clinical features, implicated drugs, diagnosis and treatment of ST are discussed. | 18,759,711 |
Investing in the future: prevention a priority at last. | We won't make progress on preventing disease if we don't try. It's time to try! | 18,759,723 |
Significantly shorter telomeres in T-cells of patients with ZAP-70+/CD38+ chronic lymphocytic leukaemia. | In contrast to other B-cell neoplasias, chronic lymphocytic leukaemia (CLL) is characterized by increased non-leukaemic T-cells. In order to assess their replicative history, telomere length was analyzed in subsets of leucocytes from CLL patients. Naive and memory T-cells from ZAP-70(+)/CD38(+) patients exhibited significantly shorter average telomere lengths than ZAP-70(-)/CD38(-) patients. Compared to the age-related percentiles of telomere length values from healthy individuals practically all values of the naive and memory T-cells from the ZAP-70(+)/CD38(+) CLL patients fell below the 50th percentile. This indicated an extensive expansion and a role for T-cells in ZAP-70(+)/CD38(+) CLL patients. | 18,759,763 |
Should we protect the strong or the weak? Risk, resilience, and the selection of marine protected areas. | It is thought that recovery of marine habitats from uncontrollable disturbance may be faster in marine reserves than in unprotected habitats. But which marine habitats should be protected, those areas at greatest risk or those at least risk? We first defined this problem mathematically for 2 alternate conservation objectives. We then analytically solved this problem for both objectives and determined under which conditions each of the different protection strategies was optimal. If the conservation objective was to maximize the chance of having at least 1 healthy site, then the best strategy was protection of the site at lowest risk. On the other hand, if the goal was to maximize the expected number of healthy sites, the optimal strategy was more complex. If protected sites were likely to spend a significant amount of time in a degraded state, then it was best to protect low-risk sites. Alternatively, if most areas were generally healthy then, counterintuitively, it was best to protect sites at higher risk. We applied these strategies to a situation of cyclone disturbance of coral reefs on Australia's Great Barrier Reef. With regard to the risk of cyclone disturbance, the optimal reef to protect differed dramatically, depending on the expected speed of reef recovery of both protected and unprotected reefs. An adequate consideration of risk is fundamental to all conservation actions and can indicate surprising routes to conservation success. | 18,759,769 |
Long-term rivastigmine treatment in a routine clinical setting. | The aim of the study was to observe the effects of long-term rivastigmine treatment in patients with mild to moderate Alzheimer's disease (AD) in a routine clinical setting. This was a prospective, open-label, observational, multicentre, non-randomized study. Outcome measures included the Mini Mental State Examination (MMSE), the Clinician's Interview-Based Impression of Change (CIBIC) and the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog). Of 217 patients initiated into rivastigmine treatment, 62% (n = 135) remained on treatment for 24 months. Most patients droped out due to nursing home placement or side effects. Eighty per cent and 67% of completers exhibited a symptomatic attenuation of cognitive decline (< or = 4-point deterioration) as assessed by using the MMSE and ADAS-cog respectively. Forty-four per cent showed an unchanged/improved CIBIC rating. Over 60% of patients remained on treatment for 2 years in this routine clinical setting. In patients who remained on treatment, rivastigmine appeared to stabilize their condition and prevented or delayed symptomatic decline. | 18,759,798 |
Don't be afraid to treat depression in patients with epilepsy! | Major depression and related depressive disorders are highly prevalent in the general population and even more so in patients with epilepsy. Yet depression in these patients remains underdiagnosed and undertreated. This is particularly worrisome as depression has greater negative impact on quality of life than seizure frequency. Additionally, depression is associated with poorer seizure control, and the risk of suicide in patients with epilepsy is greatly increased. Reluctance to treat depression results from the traditional belief that antidepressants should be restricted in epilepsy because of a supposed decrease in seizure threshold. However, there is growing evidence that many antidepressants rather have anticonvulsant effects. Experimental studies show that in critical brain regions such as the frontal lobes and the limbic system enforced serotonergic circuits increase seizure threshold. Clinical data suggest that modern antidepressants may reduce seizure frequency in patients with pharmacoresistant epilepsy. Here we review the concept that selective reuptake inhibitors of serotonin (SSRIs) have a positive effect on the mood disorder as well as on epilepsy. When adhering to the usual precautions, treatment with SSRIs in patients with epilepsy and depression is safe and should not be withheld. | 18,759,799 |
Clinical evaluation of cessation of hyperopia in 123 children with accommodative esotropia treated with glasses for best corrected vision. | This study aimed to determine age at successful cessation of hyperopic glasses, the influence of hyperopia on the esotropic angle and age at discontinuation of glasses in accommodative esotropia (AE) patients. We performed a retrospective study in 123 AE patients who achieved complete emmetropization and maintained orthophoria without hyperopic glasses between March 1999 and February 2005. All patients had been prescribed the weakest possible glasses to provide best corrected vision and maintain fusion in hyperopia. Pure AE was found in 64 patients and partial AE in 59. At the initial visit, 56.1% of patients had refractive errors of 3.00-5.00 D (mean cycloplegic spherical equivalent [SE]). The angle of esotropia without correction was 30.90 +/- 14.80 prism dioptres (PD) (mean +/- standard deviation) in pure AE, and 42.70 +/- 15.19 PD in partial AE (p = 0.000). The non-accommodative component in partial AE was 24.07 +/- 14.90 PD. The mean age at cessation of glasses use was 13.50 +/- 3.81 years. Stereopsis was noted in 70.2% of patients at the initial visit and 96.4% at the last visit. Pearson's correlation coefficients (r) were 0.480 between the degree of hyperopia and amount of optically corrected esotropia (p = 0.000), and 0.434 between the degree of hyperopia and age at successful cessation of corrective glasses use (p = 0.000). The mean age at resolution of hyperopia with good stereopsis was 13.5 years. The degree of hyperopia seemed to correlate with the angle of esotropia and the age of successful cessation of corrective glasses. | 18,759,801 |
Neuropsychological profile in bipolar disorder: a preliminary study of monotherapy lithium-treated euthymic bipolar patients evaluated at a 2-year interval. | To investigate the cognitive impairment of a sample of euthymic bipolar patients treated with lithium monotherapy at baseline in a 2-year longitudinal study. Fifteen DSM-IV-TR bipolar out-patients and 15 healthy-matched controls were cognitively assessed twice over a 2-year follow-up. All patients underwent lithium monotherapy on the first evaluation, and they were euthymic in both evaluations. Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Repeated measures multivariate analysis of variance showed that the bipolar disorder group was cognitively impaired in the executive domain, attention and processing speed, and such deficits were maintained over time. Our results showed that executive dysfunction is the main long-term neuropsychological deficit of bipolar disorder. Also, the persistence of these deficits did not seem to be influenced by any clinical or pharmacological variables. | 18,759,809 |
Investigation of the neural substrates of voice recognition in Chinese schizophrenic patients with auditory verbal hallucinations: an event-related functional MRI study. | Auditory hallucinations (AVHs), like real auditory perceptions, are often perceived as familiar voices. Given that neural correlates of AVHs involve the auditory cortex, it is likely that those brain regions responsible for recognition of voice identity are invoked during AVHs. Schizophrenic patients with (n = 13) and without (n = 13) auditory hallucinations, and 13 healthy subjects performed a voice recognition task during functional magnetic resonance imaging at 1.5 T. In the task using prerecorded vocal stimuli, they classified voice as familiar and unfamiliar. Under the familiar minus unfamiliar contrasts, cerebral activation pattern is different in the three groups and patients with auditory hallucinations showed less activation in the right temporal lobe than controls. Voice recognition was impaired in patients with AVHs. Our results support that auditory association cortices play a role in the perception of AVHs. | 18,759,811 |
Nested Markov compliance class model in the presence of time-varying noncompliance. | We consider a Markov structure for partially unobserved time-varying compliance classes in the Imbens-Rubin (1997, The Annals of Statistics 25, 305-327) compliance model framework. The context is a longitudinal randomized intervention study where subjects are randomized once at baseline, outcomes and patient adherence are measured at multiple follow-ups, and patient adherence to their randomized treatment could vary over time. We propose a nested latent compliance class model where we use time-invariant subject-specific compliance principal strata to summarize longitudinal trends of subject-specific time-varying compliance patterns. The principal strata are formed using Markov models that relate current compliance behavior to compliance history. Treatment effects are estimated as intent-to-treat effects within the compliance principal strata. | 18,759,831 |
Diagnosis of random-effect model misspecification in generalized linear mixed models for binary response. | Generalized linear mixed models (GLMMs) are widely used in the analysis of clustered data. However, the validity of likelihood-based inference in such analyses can be greatly affected by the assumed model for the random effects. We propose a diagnostic method for random-effect model misspecification in GLMMs for clustered binary response. We provide a theoretical justification of the proposed method and investigate its finite sample performance via simulation. The proposed method is applied to data from a longitudinal respiratory infection study. | 18,759,837 |
Ratio estimation with measurement error in the auxiliary variate. | With auxiliary information that is well correlated with the primary variable of interest, ratio estimation of the finite population total may be much more efficient than alternative estimators that do not make use of the auxiliary variate. The well-known properties of ratio estimators are perturbed when the auxiliary variate is measured with error. In this contribution we examine the effect of measurement error in the auxiliary variate on the design-based statistical properties of three common ratio estimators. We examine the case of systematic measurement error as well as measurement error that varies according to a fixed distribution. Aside from presenting expressions for the bias and variance of these estimators when they are contaminated with measurement error we provide numerical results based on a specific population. Under systematic measurement error, the biasing effect is asymmetric around zero, and precision may be improved or degraded depending on the magnitude of the error. Under variable measurement error, bias of the conventional ratio-of-means estimator increased slightly with increasing error dispersion, but far less than the increased bias of the conventional mean-of-ratios estimator. In similar fashion, the variance of the mean-of-ratios estimator incurs a greater loss of precision with increasing error dispersion compared with the other estimators we examine. Overall, the ratio-of-means estimator appears to be remarkably resistant to the effects of measurement error in the auxiliary variate. | 18,759,838 |
Exact confidence bounds following adaptive group sequential tests. | We provide a method for obtaining confidence intervals, point estimates, and p-values for the primary effect size parameter at the end of a two-arm group sequential clinical trial in which adaptive changes have been implemented along the way. The method is based on applying the adaptive hypothesis testing procedure of Müller and Schäfer (2001, Biometrics 57, 886-891) to a sequence of dual tests derived from the stage-wise adjusted confidence interval of Tsiatis, Rosner, and Mehta (1984, Biometrics 40, 797-803). In the nonadaptive setting this confidence interval is known to provide exact coverage. In the adaptive setting exact coverage is guaranteed provided the adaptation takes place at the penultimate stage. In general, however, all that can be claimed theoretically is that the coverage is guaranteed to be conservative. Nevertheless, extensive simulation experiments, supported by an empirical characterization of the conditional error function, demonstrate convincingly that for all practical purposes the coverage is exact and the point estimate is median unbiased. No procedure has previously been available for producing confidence intervals and point estimates with these desirable properties in an adaptive group sequential setting. The methodology is illustrated by an application to a clinical trial of deep brain stimulation for Parkinson's disease. | 18,759,843 |
A latent contingency table approach to dose finding for combinations of two agents. | Two-agent combination trials have recently attracted enormous attention in oncology research. There are several strong motivations for combining different agents in a treatment: to induce the synergistic treatment effect, to increase the dose intensity with nonoverlapping toxicities, and to target different tumor cell susceptibilities. To accommodate this growing trend in clinical trials, we propose a Bayesian adaptive design for dose finding based on latent 2 x 2 tables. In the search for the maximum tolerated dose combination, we continuously update the posterior estimates for the unknown parameters associated with marginal probabilities and the correlation parameter based on the data from successive patients. By reordering the dose toxicity probabilities in the two-dimensional space, we assign each coming cohort of patients to the most appropriate dose combination. We conduct extensive simulation studies to examine the operating characteristics of the proposed method under various practical scenarios. Finally, we illustrate our dose-finding procedure with a clinical trial of agent combinations at M. D. Anderson Cancer Center. | 18,759,848 |
Cyclo-oxygenase-1 inhibition increases acid secretion by modulating H+,K+-ATPase expression and activation in rabbit parietal cells. | 1. In the present study, we evaluated the role of cyclo-oxygenase (COX)-1 and COX-2 on gastric acid secretion in rabbit isolated parietal cells and gastric glands by examining [(14)C]-aminopyrine uptake, prostaglandin (PG) E(2) synthesis and COX-1, COX-2 and proton pump expression at baseline and after treatment with various concentrations of specific COX-1 (SC-560), COX-2 (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methyl-sulphonyl)phenyl-2 (5H)-furanone; DFU) and non-specific COX (indomethacin) inhibitors. 2. In parietal cells, SC-560 and indomethacin, over the concentration range 10(-8) to 10(-4) mol/L, dose-dependently increased basal and 10(-4) mol/L histamine-stimulated aminopyrine uptake and inhibited PGE(2) synthesis, whereas DFU (10(-8) to 10(-5) mol/L) had no effect. However, at 10(-4) mol/L, DFU augmented histamine-stimulated aminopyrine uptake by 135% and inhibited PGE(2) synthesis by 39%, indicating an inhibition of COX-1 at this higher concentration. 3. The SC-560-, DFU- and indomethacin-induced augmentation of histamine-stimulated aminopyrine uptake was reduced to basal levels after 10(-5) mol/L lansoprazole treatment in parietal cells and gastric glands, whereas 10(-4) mol/L ranitidine only partially inhibited such augmentation. 4. Only COX-1 was detected in parietal cells. However, both COX-1 and COX-2 were expressed in gastric glands, with relative protein density of COX-1 being sixfold higher than that of COX-2. Protein levels of COX-1 in parietal cells and those of COX-1 and COX-2 in gastric glands remained unchanged, regardless of inhibitor treatment, either alone or with histamine. 5. Parietal cell proton pump expression was significantly enhanced by 10(-5) mol/L SC-560 and 10(-4) mol/L indomethacin (by 29 and 31%, respectively) and pump activity was enhanced by 61 and 65%, respectively. In contrast, 10(-5) mol/L DFU had no effect. 6. In conclusion, the data indicate that inhibition of COX-1- but not COX-2-derived PGE(2) synthesis is involved in augmentation of non-steroidal anti-inflammatory drug-induced gastric acid secretion in parietal cells by enhancing expression and activation of the proton pump. | 18,759,857 |
The validity and reliability of the occupational contact dermatitis disease severity index. | The occupational contact dermatitis disease severity index (ODDI) was designed to assess the severity and importantly the functional disability caused by occupational contact dermatitis (OCD) of the hands in patients attending our occupational dermatology clinic. To investigate the accuracy of the ODDI. Of 205 patients, 95 were assessed as having OCD of the hands. Content validity was assessed by content mapping and expert opinion. Construct validity was examined through comparing the ODDI against global clinical dermatology severity assessment (GCDSA). Intraobserver reliability, interobserver reliability, internal consistency, acceptability and convenience were also assessed. The ODDI was found to have content validity by the experts and was moderately correlated with GCDSA, supporting construct validity (Pearson's r = 0.54; P < or = 0.01). The ODDI was shown to be reliable with substantial agreement for both intraobserver reliability [intraclass correlation coefficient (ICC) = 0.62] and interobserver reliability (ICC = 0.75). Internal consistency within the ODDI was almost perfect (ICC = 0.94-0.99) and user survey showed the ODDI to be acceptable, easy and quick to use. The ODDI is a valid and reliable instrument to assess the severity and functional limitations caused by OCD, in patients who have had treatment or modified work duties, associated with some improvement of their dermatitis. | 18,759,896 |
Regulation of hematopoietic cell function by inhibitory immunoglobulin G receptors and their inositol lipid phosphatase effectors. | Numerous autoimmune and inflammatory disorders stem from the dysregulation of hematopoietic cell activation. The activity of inositol lipid and protein tyrosine phosphatases, and the receptors that recruit them, is critical for prevention of these disorders. Balanced signaling by inhibitory and activating receptors is now recognized to be an important factor in tuning cell function and inflammatory potential. In this review, we provide an overview of current knowledge of membrane proximal events in signaling by inhibitory/regulatory receptors focusing on structural and functional characteristics of receptors and their effectors Src homology 2 (SH2) domain-containing tyrosine phosphatase 1 and SH2 domain-containing inositol 5-phosphatase-1. We review use of new strategies to identify novel regulatory receptors and effectors. Finally, we discuss complementary actions of paired inhibitory and activating receptors, using Fc gammaRIIA and Fc gammaRIIB regulation human basophil activation as a prototype. | 18,759,919 |
Putting out the fire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins. | The mounting of an effective immune response requires the coordinated function of both the innate and the adaptive arm of the immune system. Cells from both types of immunity respond to antigenic stimuli through a variety of surface and intracellular receptors and produce cytokines that tightly orchestrate the inflammatory response. The operation of feedback control mechanisms that regulate the duration and the amplitude of antigenic and cytokine receptor signaling is therefore required to prevent hyper-activation of the immune system that could lead to tissue destruction or autoimmunity. Suppressor of cytokine signaling (SOCS) proteins have been identified as a negative feedback loop to cytokine signaling. Recently, the generation of genetically engineered mouse models permitted the evaluation of their function in different processes of the immune responses. In this article, we review new insights into the modular structure of SOCS proteins and the function of SOCS1 and SOCS3 to negatively regulate activation and/or differentiation pathways in macrophages, dendritic cells, and T lymphocytes. Thus, SOCS family proteins are components of an emerging immunoregulatory mechanism that maintains the coordinated balance of both innate and adaptive immune responses. | 18,759,933 |
Reduced activation in right lateral prefrontal cortex and anterior cingulate gyrus in medication-naïve adolescents with attention deficit hyperactivity disorder during time discrimination. | Patients with attention deficit hyperactivity disorder (ADHD) under-perform when discriminating between durations differing by several hundred milliseconds. This function involves right prefrontal and anterior cingulate (AC) brain regions, which are structurally and functionally compromised in this patient group during executive tasks. We investigated the neuro-anatomical substrates mediating fine temporal discrimination in adolescents with ADHD compared with controls, using functional magnetic resonance imaging (fMRI). Twenty-one male medication-naïve adolescents aged 10-15 years with a DSM-IV diagnosis of ADHD (combined subtype) and without comorbid Axis I disorders (except conduct disorder) were compared to a group of 17 age- and IQ-matched healthy adolescents. Using fMRI on a 1.5T scanner, we compared brain activation and performance between adolescents with ADHD and controls during a time discrimination task contrasted with a temporal order task. Despite comparable performance, patients with ADHD showed decreased activation in right dorsolateral and inferior prefrontal cortex and AC during time discrimination compared with controls. Right hemispheric fronto-cingulate abnormalities in ADHD, previously observed during inhibitory and executive functions, are also associated with temporal perception. Furthermore, recruitment of medication-naïve patients precludes the possibility that deficits are attributable to stimulant exposure. | 18,759,938 |
Factors associated with knowledge of genetics and nutritional genomics among dietitians. | Knowledge of genetics and nutritional genomics is important for dietitians in the prevention and management of disease. The present study aimed to analyse data from a nationwide postal questionnaire survey in order to investigate the factors associated with knowledge of genetics and nutritional genomics among dietitians in the UK. A nationwide postal questionnaire survey was conducted in a random sample of 600 dietitians in the UK. The questionnaire measured dietitians' knowledge using 12 multiple choice questions relating to genetics and nutritional genomics. Factors that may impact upon such knowledge were also recorded. Knowledge scores were calculated and compared between dietitians using comparative statistics and univariate analysis of variance. A total of 389 (64.8%) usable questionnaires were returned. Overall, the mean +/- SD total knowledge score was low at 41 +/- 19%. Highest qualification (F(2,372) = 9.1, P < 0.001), the genetics content of university education (F(2,372) = 7.1, P = 0.001) and reading literature or attending a conference relating to genetics or nutritional genomics within the last year (F(1,372) = 11.9, P = 0.001) were all associated with higher total knowledge scores. Knowledge of genetics and nutritional genomics among dietitians is currently low, and better knowledge is associated with exposure to these in university education and continuing professional development. | 18,759,954 |
Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial. | Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation < or = 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis--undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital--thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups. (Trial registration: US Clinical Trials registry NCT00622570.). | 18,759,980 |
"Hook"-calibration of GeneChip-microarrays: chip characteristics and expression measures. | Microarray experiments rely on several critical steps that may introduce biases and uncertainty in downstream analyses. These steps include mRNA sample extraction, amplification and labelling, hybridization, and scanning causing chip-specific systematic variations on the raw intensity level. Also the chosen array-type and the up-to-dateness of the genomic information probed on the chip affect the quality of the expression measures. In the accompanying publication we presented theory and algorithm of the so-called hook method which aims at correcting expression data for systematic biases using a series of new chip characteristics. In this publication we summarize the essential chip characteristics provided by this method, analyze special benchmark experiments to estimate transcript related expression measures and illustrate the potency of the method to detect and to quantify the quality of a particular hybridization. It is shown that our single-chip approach provides expression measures responding linearly on changes of the transcript concentration over three orders of magnitude. In addition, the method calculates a detection call judging the relation between the signal and the detection limit of the particular measurement. The performance of the method in the context of different chip generations and probe set assignments is illustrated. The hook method characterizes the RNA-quality in terms of the 3'/5'-amplification bias and the sample-specific calling rate. We show that the proper judgement of these effects requires the disentanglement of non-specific and specific hybridization which, otherwise, can lead to misinterpretations of expression changes. The consequences of modifying probe/target interactions by either changing the labelling protocol or by substituting RNA by DNA targets are demonstrated. The single-chip based hook-method provides accurate expression estimates and chip-summary characteristics using the natural metrics given by the hybridization reaction with the potency to develop new standards for microarray quality control and calibration. | 18,759,984 |
Effect of sperm parameters on intrauterine insemination pregnancy rate. | To assess the effect of sperm parameters on pregnancy rate following Intrauterine Insemination (IUI) in primary and secondary infertile patients. An observational study. The Assisted Conception Unit, Department of Obstetrics and Gynaecology, Services Institute of Medical Sciences, Lahore, Pakistan, from January 2004 to January 2006. One hundred and thirty-six couples, comprising 110 couples with primary and 26 with secondary infertility, of at least one year of infertility, were studied. All underwent a total of 231 intrauterine insemination cycles. A detailed history for infertility evaluation was taken. Hormonal profiles were done on day two of the menstrual cycle. Ovarian stimulation of all patients with Clomiphene citrate was done from day two of the menstrual cycle for 5 days and subsequent transvaginal scans on day twelve, for follicular tracking were done. Semen analysis was done, after 2-3 days abstinence and sperms for intrauterine insemination were prepared according to Density Gradient Sperm Wash Method. IUI was done 36 hours after tracking of the dominant follicles and injection hCG was given for follicular maturation and rupture. The main outcome measures were determining the effect of normal and abnormal sperm parameters on pregnancy outcome, in ovulation induced infertile couples, undergoing intrauterine insemination cycles. Of the 136 couples, who underwent IUI cycles, 18 had male factor infertility and the rest were with normal semen parameters. An IUI pregnancy rate of 13.7% was seen with a total of 4 conceptions. This study confirms that IUI, because of its cost effectiveness and minimum complications, can be applied as a first line treatment in infertile couples after considering the sperm parameters. | 18,760,044 |
Hypereosinophilic syndrome causing acute hemiplegia in childhood. | Hypereosinophilic syndrome (HES) is a rare heterogeneous group of disorders, characterized by marked peripheral blood and tissue eosinophilia resulting in end organ damage. This case describes a six-year-old girl child who presented with sudden weakness of right half of body and fever. Computed tomogram of brain showed infarction of left internal capsule and basal ganglia. She had peripheral and bone marrow eosinophilia. No other cause was found for infarction. | 18,760,055 |
Perineal ectopic testis - a rare encounter in paediatric surgical practice. | Perineal ectopic testis is a rare form of testicular maldescent. We report 2 patients with perineal ectopic testes, in one of them, the condition was bilateral (only the 6th case of this variety). Surgery was performed in both cases and testicles were mobilized and fixed in the scrotum. Gubernaculum testis was found to be fixed in the perineum. Examination of patient with empty scrotum (maldescent testes) should include examination of sites like perineum to look for ectopic testis. | 18,760,056 |
Bouveret's syndrome. | Gastric Outlet Obstruction (GOO) due to impaction of a gallstone in the duodenum after migration through a bilioduodenal fistula is known as Bouveret's syndrome. Its clinical symptoms are entirely vague and nonspecific. Because of its rarity, insidiousness and unpredictable symptomatology, Bouveret's syndrome is never thought of in the differential diagnosis as aetiology of gastric outlet obstruction. Recent advances in fiberoptics technology, advent of modern imaging modalities and minimally-invasive techniques like endoscopy and laparoscopy has brought a great revolution in the management of Bouveret's syndrome and have tremendously decreased morbidity and mortality associated with this rare clinical entity. | 18,760,069 |
Complete Androgen Insensitivity Syndrome. | The incidence of Complete Androgen Insensitivity Syndrome (CAIS) is about 1 in 20,000. People with CAIS are normal appearing females, despite the presence of testes and a 46, XY chromosome constitution. We came across a case in which a 17 years old girl presented with the complaint of inguinal hernia and amenorrhea. Subsequent investigations were done revealing absence of female internal genitalia and the presence of abdominal mass, possibly testes. Syndrome has been linked to mutations in AR, the gene for the human Androgen Receptor, located at Xq11-12 leading to the insensitivity of the receptor to testosterone. Gonadectomy was performed and life long Hormone replacement therapy was advised. | 18,760,072 |
[Infectious complications of surgically treatment pelvic fractures]. | Based on case histories, the authors draw attention to important infectious complications in patients surgically treated for pelvic injuries. These complications were recorded in four out of 75 patients (5.3%) undergoing surgery for pelvic fracture in the period from 2001 to 2005. The chief risk factors for the development of infection included the poor state of health of a polytraumatized patient in combination with a long stay in an acute care unit, and severe trauma and bleeding of soft tissue structures in B and C types of pelvic injury. Bacteriological findings showed the presence of several pathogenic species (Enterobacter cloacae, Citrobacter koseri, Pseudomonas aeruginosa and Klebsiella oxytoca) or multi-resistant bacteria (methicillin-resistant Staphylococcus aureus). | 18,760,086 |
Current role of sodium bicarbonate-based preprocedural hydration for the prevention of contrast-induced acute kidney injury: a meta-analysis. | The optimal hydration strategy for prevention of contrast-induced acute kidney injury (AKI) remains unknown. The purpose of this meta-analysis is to compare the effectiveness of normal saline (NS) versus sodium bicarbonate hydration (NaHCO(3)) for prevention of contrast-induced AKI. We performed a meta-analysis of randomized controlled trials that compared saline-based hydration with sodium bicarbonate-based hydration regimen for prophylaxis of contrast-induced AKI. The literature search included MEDLINE, EMBASE, and Cochrane databases (2000 to October 2007); conference proceedings; and bibliographies of retrieved articles. Information was extracted on study design, sample characteristics, and interventions. Random-effects models were used to calculate summary risk ratios for contrast-induced AKI, need for hemodialysis, and death. Seven trials with 1,307 subjects were included. Preprocedural hydration with sodium bicarbonate was associated with a significant decrease in the rate of contrast-induced AKI (5.96% in the NaHCO(3) arm versus 17.23% in the NS arm, summary risk ratio 0.37, 95% CI 0.18-0.714, P = .005). There was no difference in the rates of postprocedure hemodialysis or death. Formal testing revealed moderate heterogeneity and a strong likelihood of publication bias. Although sodium bicarbonate hydration was found to be superior to NS in prevention of contrast-induced AKI, these results are in the context of study heterogeneity and, likely, publication bias. An adequately powered randomized controlled trial is warranted to define the optimal hydration strategy in patients at high risk of contrast-induced AKI who are scheduled to undergo contrast administration. | 18,760,120 |
Treatment of chronic systolic heart failure secondary to Chagas heart disease in the current era of heart failure therapy. | The treatment of chronic heart failure secondary to Chagas disease has been based on extrapolation of data achieved in the treatment of non-Chagas disease heart failure. Because beta-blockers decrease the incidence of sudden cardiac death in non-Chagas disease heart failure and sudden cardiac death occurs preferentially in patients with mild Chagas disease heart failure, beta-blockers may be administered first to class I/II patients with Chagas disease heart failure. In advanced Chagas disease heart failure, angiotensin-converting enzyme inhibitor and diuretics may be given at first to compensate for congestive symptoms. After clinical status improvement, beta-blockers should be given at targeted doses, if necessary reducing angiotensin-converting enzyme inhibitor doses. Primary and secondary prevention of sudden cardiac death may be accomplished with implantable cardioverter defibrillators because of the high recurrence of life-threatening arrhythmias despite amiodarone administration. In refractory heart failure, heart transplantation is the treatment of choice. | 18,760,121 |
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